VCV002430184.3 - ClinVar

NM_002437.5(MPV17):c.210C>A (p.Tyr70Ter)

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.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002437.5(MPV17):c.210C>A (p.Tyr70Ter)

Variation ID: 2430184 Accession: VCV002430184.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p23.3 2: 27312749 (GRCh38) [ NCBI UCSC ] 2: 27535616 (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	Feb 25, 2023	Oct 8, 2024	Dec 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_002437.5:c.210C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002428.1:p.Tyr70Ter	nonsense
NM_002437.4:c.210C>A
NC_000002.12:g.27312749G>T
NC_000002.11:g.27535616G>T
NG_008075.1:g.14816C>A
NG_008075.2:g.15348C>A
NG_033055.1:g.515C>A
NG_033055.2:g.696C>A

... more HGVS ... less HGVS

Protein change

Y70*

Other names

Canonical SPDI

NC_000002.12:27312748:G:T

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.
MPV17		-	-	GRCh38 GRCh37	321	351
UCN		-	-	GRCh38 GRCh37	11	30

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.
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)	Pathogenic (1)	criteria provided, single submitter	Feb 23, 2023	RCV003128210.2
not provided	Pathogenic (1)	criteria provided, single submitter	Dec 14, 2023	RCV003575036.2
MPV17-related disorder	Likely pathogenic (1)	no assertion criteria provided	Mar 22, 2024	RCV004733612.1

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.
Pathogenic (Feb 23, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV003804386.1 First in ClinVar: Feb 25, 2023 Last updated: Feb 25, 2023	Clinical Features: Biliary tract abnormality (present) , Acidosis (present) , Metabolic acidosis (present) , Hypoglycemia (present) , Abnormality of mitochondrial metabolism (present) , Acute liver failure (present)
Pathogenic (Dec 14, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004364013.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 23714749 Comment: This sequence change creates a premature translational stop signal (p.Tyr70) in the MPV17 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Tyr70) in the MPV17 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MPV17-related conditions. ClinVar contains an entry for this variant (Variation ID: 2430184). For these reasons, this variant has been classified as Pathogenic. (less)
Likely pathogenic (Mar 22, 2024)	no assertion criteria provided Method: clinical testing	MPV17-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005341069.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: The MPV17 c.210C>A variant is predicted to result in premature protein termination (p.Tyr70). To our knowledge, this variant has not been reported in the literature. … (more) The MPV17 c.210C>A variant is predicted to result in premature protein termination (p.Tyr70). To our knowledge, this variant has not been reported in the literature. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in MPV17 are expected to be pathogenic. This variant is interpreted as likely pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Tyr70*) in the MPV17 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MPV17-related conditions. ClinVar contains an entry for this variant (Variation ID: 2430184). For these reasons, this variant has been classified as Pathogenic.

Comment:

The MPV17 c.210C>A variant is predicted to result in premature protein termination (p.Tyr70*). To our knowledge, this variant has not been reported in the literature. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in MPV17 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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

Title	Author	Journal	Year	Link
Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene.	Uusimaa J	European journal of human genetics : EJHG	2014	PMID: 23714749

Text-mined citations for this variant ...

Record last updated Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_002437.5(MPV17):c.210C>A (p.Tyr70Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...