VCV000561179.3 - ClinVar

NM_015294.6(TRIM37):c.586C>T (p.Gln196Ter)

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.

(3)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_015294.6(TRIM37):c.586C>T (p.Gln196Ter)

Variation ID: 561179 Accession: VCV000561179.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q22 17: 59079784 (GRCh38) [ NCBI UCSC ] 17: 57157145 (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	Sep 16, 2018	Oct 8, 2024	Oct 12, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_015294.6:c.586C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_056109.1:p.Gln196Ter	nonsense
NM_001005207.5:c.586C>T	NP_001005207.1:p.Gln196Ter	nonsense
NM_001320987.3:c.484C>T	NP_001307916.1:p.Gln162Ter	nonsense
NM_001320988.3:c.586C>T	NP_001307917.1:p.Gln196Ter	nonsense
NM_001320989.3:c.586C>T	NP_001307918.1:p.Gln196Ter	nonsense
NM_001320990.3:c.220C>T	NP_001307919.1:p.Gln74Ter	nonsense
NM_001353082.2:c.484C>T	NP_001340011.1:p.Gln162Ter	nonsense
NM_001353083.2:c.-167C>T		5 prime UTR
NM_001353084.2:c.586C>T	NP_001340013.1:p.Gln196Ter	nonsense
NM_001353085.2:c.124C>T	NP_001340014.1:p.Gln42Ter	nonsense
NM_001353086.2:c.586C>T	NP_001340015.1:p.Gln196Ter	nonsense
NR_148346.2:n.1005C>T		non-coding transcript variant
NR_148347.2:n.903C>T		non-coding transcript variant
NC_000017.11:g.59079784G>A
NC_000017.10:g.57157145G>A
NG_009298.1:g.32122C>T

... more HGVS ... less HGVS

Protein change

Q196*, Q42*, Q74*, Q162*

Other names

Canonical SPDI

NC_000017.11:59079783:G:A

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

protein truncation; Variation Ontology [ VariO:0015]

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

dbSNP: rs1568191596 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.
TRIM37		-	-	GRCh38 GRCh37	713	786

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.
Mulibrey nanism syndrome	Likely pathogenic (3)	criteria provided, single submitter	Oct 12, 2023	RCV000680212.3

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.
Likely pathogenic (Oct 12, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mulibrey nanism syndrome Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004204297.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Uncertain significance (-)	no assertion criteria provided Method: reference population	Mulibrey nanism syndrome Affected status: unknown Allele origin: germline	Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology Accession: SCV000803653.1 First in ClinVar: Sep 16, 2018 Last updated: Sep 16, 2018	Number of individuals with the variant: 1 Sex: mixed Geographic origin: Russia
Likely pathogenic (Jul 16, 2024)	no assertion criteria provided Method: clinical testing	Mulibrey nanism syndrome (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Genetics laboratory, Department of Obstetrics & Gynae, Institute of Kidney Diseases & Research Centre Dr. H.L. Trivedi Institute Of Transplantation Sciences Accession: SCV005326559.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: A homozygous nonsense variant c.586C>T in TRIM37 gene (chr17:57157145; Depth:63x) was detected. The variant (p.Gln196Ter) at 196th amino acid position, the glutamine is replaced by … (more) A homozygous nonsense variant c.586C>T in TRIM37 gene (chr17:57157145; Depth:63x) was detected. The variant (p.Gln196Ter) at 196th amino acid position, the glutamine is replaced by a premature stop codon. This variant has not been observed in the 1000 genomes and topmed database but has a minor allele frequency in the gnomAD database. The variant has been reported as likely pathogenic in clinvar database. In silico predictions are deleterious by SIFT, PolyPhen2, CADD, REVEL and MVP. Based on the aforementioned evidence, the variant is classified as a likely pathogenic according to the ACMG-AMP classification system. (less) Clinical Features: Bilateral undescended testis (present) , Short stature (present) , Dysmorphic facies (present) , Congenital heart disease (present) , Normal milestones achieved (present) , leg weakness … (more) Bilateral undescended testis (present) , Short stature (present) , Dysmorphic facies (present) , Congenital heart disease (present) , Normal milestones achieved (present) , leg weakness (present) , mild hypotonia (present) (less) Indication for testing: Russell-Silver syndrome Age: 0-9 years Sex: male Ethnicity/Population group: Hindu Geographic origin: India Comment on evidence: bilateral undescended testis, short stature, dysmorphic facial features, and a congenital cardiac anomaly, WES analysis Testing laboratory: Institute of Kidney Disease & Research Centre Date variant was reported to submitter: 2024-07-16 Testing laboratory interpretation: Likely pathogenic

Comment:

A homozygous nonsense variant c.586C>T in TRIM37 gene (chr17:57157145; Depth:63x) was detected. The variant (p.Gln196Ter) at 196th amino acid position, the glutamine is replaced by a premature stop codon. This variant has not been observed in the 1000 genomes and topmed database but has a minor allele frequency in the gnomAD database. The variant has been reported as likely pathogenic in clinvar database. In silico predictions are deleterious by SIFT, PolyPhen2, CADD, REVEL and MVP. Based on the aforementioned evidence, the variant is classified as a likely pathogenic according to the ACMG-AMP classification system.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
protein truncation			Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology Accession: SCV000803653.1

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 rs1568191596 ...

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 08, 2024

ClinVar Genomic variation as it relates to human health

NM_015294.6(TRIM37):c.586C>T (p.Gln196Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1568191596 ...