VCV000214127.2 - ClinVar

NM_001195248.2(APTX):c.814T>C (p.Cys272Arg)

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.

(1)

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001195248.2(APTX):c.814T>C (p.Cys272Arg)

Variation ID: 214127 Accession: VCV000214127.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9p21.1 9: 32974518 (GRCh38) [ NCBI UCSC ] 9: 32974516 (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	Oct 11, 2015	Oct 11, 2015	Feb 18, 2013

HGVS

Nucleotide	Protein	Molecular consequence
NM_001195248.2:c.814T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001182177.2:p.Cys272Arg	missense
NM_001195249.2:c.814T>C	NP_001182178.1:p.Cys272Arg	missense
NM_001195250.2:c.652T>C	NP_001182179.2:p.Cys218Arg	missense
NM_001195251.2:c.814T>C	NP_001182180.1:p.Cys272Arg	missense
NM_001195252.2:c.598T>C	NP_001182181.2:p.Cys200Arg	missense
NM_001195254.2:c.652T>C	NP_001182183.1:p.Cys218Arg	missense
NM_001368995.1:c.814T>C	NP_001355924.1:p.Cys272Arg	missense
NM_001368996.1:c.814T>C	NP_001355925.1:p.Cys272Arg	missense
NM_001368997.1:c.814T>C	NP_001355926.1:p.Cys272Arg	missense
NM_001368998.1:c.814T>C	NP_001355927.1:p.Cys272Arg	missense
NM_001368999.1:c.814T>C	NP_001355928.1:p.Cys272Arg	missense
NM_001369000.1:c.652T>C	NP_001355929.1:p.Cys218Arg	missense
NM_001369001.1:c.652T>C	NP_001355930.1:p.Cys218Arg	missense
NM_001369002.1:c.550T>C	NP_001355931.1:p.Cys184Arg	missense
NM_001369003.1:c.550T>C	NP_001355932.1:p.Cys184Arg	missense
NM_001369004.1:c.550T>C	NP_001355933.1:p.Cys184Arg	missense
NM_001369005.1:c.550T>C	NP_001355934.1:p.Cys184Arg	missense
NM_001369006.1:c.550T>C	NP_001355935.1:p.Cys184Arg	missense
NM_001370669.1:c.550T>C	NP_001357598.1:p.Cys184Arg	missense
NM_001370670.1:c.550T>C	NP_001357599.1:p.Cys184Arg	missense
NM_001370673.1:c.550T>C	NP_001357602.1:p.Cys184Arg	missense
NM_175069.3:c.814T>C	NP_778239.2:p.Cys272Arg	missense
NM_175073.3:c.814T>C	NP_778243.1:p.Cys272Arg	missense
NR_036577.2:n.765T>C		non-coding transcript variant
NR_160920.1:n.653T>C		non-coding transcript variant
NR_160921.1:n.784T>C		non-coding transcript variant
NR_160922.1:n.1015T>C		non-coding transcript variant
NR_160923.1:n.819T>C		non-coding transcript variant
NR_160924.1:n.824T>C		non-coding transcript variant
NR_160925.1:n.1020T>C		non-coding transcript variant
NR_160926.1:n.810T>C		non-coding transcript variant
NR_160927.1:n.903T>C		non-coding transcript variant
NR_160928.1:n.793T>C		non-coding transcript variant
NR_160929.1:n.707T>C		non-coding transcript variant
NR_160930.1:n.760T>C		non-coding transcript variant
NR_160931.1:n.999T>C		non-coding transcript variant
NC_000009.12:g.32974518A>G
NC_000009.11:g.32974516A>G
NG_012821.2:g.55614T>C

... more HGVS ... less HGVS

Protein change

C272R, C184R, C218R, C200R

Other names

p.C272R:TGC>CGC

Canonical SPDI

NC_000009.12:32974517:A: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.

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

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

ClinGen: CA320306 dbSNP: rs144893610 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.
APTX		-	-	GRCh38 GRCh37	289	358

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	Uncertain significance (1)	criteria provided, single submitter	Feb 18, 2013	RCV000195919.1

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 (Feb 18, 2013)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000251158.11 First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015	Comment: p.Cys272Arg (TGC>CGC): c.814 T>C in exon 8 of the APTX gene (NM_175073.2). The C272Rmissense substitution has not been published as a mutation, nor has it … (more) p.Cys272Arg (TGC>CGC): c.814 T>C in exon 8 of the APTX gene (NM_175073.2). The C272Rmissense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. C272R is a non-conservative amino acid substitution as an uncharged Cysteine residue involved in disulfide bonding is replaced with a positively charged Arginine residue at a position in the APTX protein that is conserved across species. Missense mutations in neighboring codons (D276G and W279R) have been reported in the literature in association with ataxia-ocular apraxia 1; however, multiple in-silico prediction algorithms predict that C272 is a benign change. Therefore, based on the currently available information, it is unclear whether C272R is a disease-causing mutation or a rare benign variant. The variant is found in LSME-MITOP panel(s). (less)

Comment:

p.Cys272Arg (TGC>CGC): c.814 T>C in exon 8 of the APTX gene (NM_175073.2). The C272Rmissense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. C272R is a non-conservative amino acid substitution as an uncharged Cysteine residue involved in disulfide bonding is replaced with a positively charged Arginine residue at a position in the APTX protein that is conserved across species. Missense mutations in neighboring codons (D276G and W279R) have been reported in the literature in association with ataxia-ocular apraxia 1; however, multiple in-silico prediction algorithms predict that C272 is a benign change. Therefore, based on the currently available information, it is unclear whether C272R is a disease-causing mutation or a rare benign variant. The variant is found in LSME-MITOP panel(s).

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 rs144893610 ...

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 Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_001195248.2(APTX):c.814T>C (p.Cys272Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs144893610 ...