VCV000432628.37 - ClinVar

NM_001170535.3(ATAD3A):c.229C>G (p.Leu77Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(7)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(5)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001170535.3(ATAD3A):c.229C>G (p.Leu77Val)

Variation ID: 432628 Accession: VCV000432628.37

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p36.33 1: 1516035 (GRCh38) [ NCBI UCSC ] 1: 1451415 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 20, 2017	Oct 20, 2024	Oct 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001170535.3:c.229C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001164006.1:p.Leu77Val	missense
NM_001170536.3:c.-9C>G		5 prime UTR
NM_018188.5:c.229C>G	NP_060658.3:p.Leu77Val	missense
NC_000001.11:g.1516035C>G
NC_000001.10:g.1451415C>G
NG_053035.1:g.8893C>G

... more HGVS ... less HGVS

Protein change

L77V

Other names

Canonical SPDI

NC_000001.11:1516034:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Trans-Omics for Precision Medicine (TOPMed) 0.00039

The Genome Aggregation Database (gnomAD) 0.00040

Exome Aggregation Consortium (ExAC) 0.00042

The Genome Aggregation Database (gnomAD), exomes 0.00043

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054

Links

ClinGen: CA525640 dbSNP: rs138594222 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ATAD3A		-	-	GRCh38 GRCh37	291	461

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Oct 1, 2023	RCV000498349.27
Harel-Yoon syndrome	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Oct 28, 2019	RCV001249364.5
Harel-Yoon syndrome Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal	Uncertain significance (1)	criteria provided, single submitter	Jul 30, 2021	RCV002489219.2
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Jun 29, 2021	RCV004023340.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Oct 28, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Harel-Yoon syndrome Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001369491.2 First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020	Comment: This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in … (more) This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PM3. This variant was detected in homozygous state. (less)
Uncertain significance (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Harel-Yoon syndrome (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Hadassah Hebrew University Medical Center Accession: SCV001468306.1 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021
Uncertain significance (Dec 18, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000590377.4 First in ClinVar: Aug 20, 2017 Last updated: Sep 24, 2021	Comment: In silico analysis supports that this missense variant does not alter protein structure/function
Uncertain significance (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Harel-Yoon syndrome Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002783950.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Jun 29, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV004910689.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.229C>G (p.L77V) alteration is located in exon 2 (coding exon 2) of the ATAD3A gene. This alteration results from a C to G substitution … (more) The c.229C>G (p.L77V) alteration is located in exon 2 (coding exon 2) of the ATAD3A gene. This alteration results from a C to G substitution at nucleotide position 229, causing the leucine (L) at amino acid position 77 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Pathogenic (Oct 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001370921.24 First in ClinVar: Jul 16, 2020 Last updated: Oct 20, 2024	Comment: ATAD3A: PM3:Very Strong, PM2, PM5 Number of individuals with the variant: 6
not provided (-)	no classification provided Method: phenotyping only	Harel-Yoon syndrome Affected status: unknown Allele origin: germline	GenomeConnect, ClinGen Accession: SCV001423351.1 First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020	Comment: Variant interpretted as Uncertain significance and reported on 10-07-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the … (more) Variant interpretted as Uncertain significance and reported on 10-07-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less) Clinical Features: Hyperthyroidism (present) , Hypermetropia (present) , Abnormality of the somatic nervous system (present) , Abnormality of the musculature of the limbs (present) , Abnormal renal … (more) Hyperthyroidism (present) , Hypermetropia (present) , Abnormality of the somatic nervous system (present) , Abnormality of the musculature of the limbs (present) , Abnormal renal morphology (present) (less) Indication for testing: Diagnostic Age: 50-59 years Sex: female Testing laboratory: GeneDx Date variant was reported to submitter: 2018-10-07 Testing laboratory interpretation: Uncertain significance

Comment:

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PM3. This variant was detected in homozygous state.

Comment:

The c.229C>G (p.L77V) alteration is located in exon 2 (coding exon 2) of the ATAD3A gene. This alteration results from a C to G substitution at nucleotide position 229, causing the leucine (L) at amino acid position 77 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

Variant interpretted as Uncertain significance and reported on 10-07-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs138594222 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001170535.3(ATAD3A):c.229C>G (p.Leu77Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs138594222 ...