VCV001806211.4 - ClinVar

NM_004279.3(PMPCB):c.122G>A (p.Arg41Lys)

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.

(2)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004279.3(PMPCB):c.122G>A (p.Arg41Lys)

Variation ID: 1806211 Accession: VCV001806211.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.1 7: 103298590 (GRCh38) [ NCBI UCSC ] 7: 102939037 (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	Dec 24, 2022	May 1, 2024	Jul 9, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_004279.3:c.122G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004270.2:p.Arg41Lys	missense
NC_000007.14:g.103298590G>A
NC_000007.13:g.102939037G>A

Protein change

R41K

Other names

Canonical SPDI

NC_000007.14:103298589:G:A

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.

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

Links

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.
PMPCB		-	-	GRCh38 GRCh37	114	185

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.
Multiple mitochondrial dysfunctions syndrome 6	Uncertain significance (1)	criteria provided, single submitter	Aug 28, 2019	RCV002470495.1
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Jul 9, 2021	RCV002571490.2

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 (Aug 28, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Multiple mitochondrial dysfunctions syndrome 6 (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002768014.1 First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022	Comment: A heterozygous missense variant was identified, NM_004279.2(PMPCB):c.122G>A in exon 2 of 13 of the PMPCB gene. This substitution is predicted to create a minor amino … (more) A heterozygous missense variant was identified, NM_004279.2(PMPCB):c.122G>A in exon 2 of 13 of the PMPCB gene. This substitution is predicted to create a minor amino acid change from arginine to lysine at position 41 of the protein, NP_004270.2(PMPCB):p.(Arg41Lys). The arginine at this position has low conservation (100 vertebrates, UCSC). It is located within the mitochondrial targeting sequence. In silico software predicts this variant to be benign (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.001% (4 heterozygotes, 0 homozygotes). The variant has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). (less)
Uncertain significance (Jul 09, 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: SCV003705123.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: The c.122G>A (p.R41K) alteration is located in exon 2 (coding exon 2) of the PMPCB gene. This alteration results from a G to A substitution … (more) The c.122G>A (p.R41K) alteration is located in exon 2 (coding exon 2) of the PMPCB gene. This alteration results from a G to A substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)

Comment:

A heterozygous missense variant was identified, NM_004279.2(PMPCB):c.122G>A in exon 2 of 13 of the PMPCB gene. This substitution is predicted to create a minor amino acid change from arginine to lysine at position 41 of the protein, NP_004270.2(PMPCB):p.(Arg41Lys). The arginine at this position has low conservation (100 vertebrates, UCSC). It is located within the mitochondrial targeting sequence. In silico software predicts this variant to be benign (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.001% (4 heterozygotes, 0 homozygotes). The variant has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).

Comment:

The c.122G>A (p.R41K) alteration is located in exon 2 (coding exon 2) of the PMPCB gene. This alteration results from a G to A substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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 this variant ...

Record last updated May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_004279.3(PMPCB):c.122G>A (p.Arg41Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...