NM_001195248.2(APTX):c.953G>A (p.Arg318His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 17, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000351313.5

Allele description [Variation Report for NM_001195248.2(APTX):c.953G>A (p.Arg318His)]

NM_001195248.2(APTX):c.953G>A (p.Arg318His)

Gene:

APTX:aprataxin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p21.1

Genomic location:

Preferred name:

NM_001195248.2(APTX):c.953G>A (p.Arg318His)

HGVS:

NC_000009.12:g.32973574C>T
NG_012821.2:g.56558G>A
NM_001195248.2:c.953G>AMANE SELECT
NM_001195249.2:c.953G>A
NM_001195250.2:c.791G>A
NM_001195251.2:c.*110G>A
NM_001195252.2:c.737G>A
NM_001195254.2:c.791G>A
NM_001368995.1:c.953G>A
NM_001368996.1:c.953G>A
NM_001368997.1:c.953G>A
NM_001368998.1:c.953G>A
NM_001368999.1:c.*110G>A
NM_001369000.1:c.791G>A
NM_001369001.1:c.791G>A
NM_001369002.1:c.689G>A
NM_001369003.1:c.689G>A
NM_001369004.1:c.689G>A
NM_001369005.1:c.689G>A
NM_001369006.1:c.*110G>A
NM_001370669.1:c.689G>A
NM_001370670.1:c.689G>A
NM_001370673.1:c.689G>A
NM_175069.3:c.*110G>A
NM_175073.3:c.953G>A
NP_001182177.2:p.Arg318His
NP_001182178.1:p.Arg318His
NP_001182179.2:p.Arg264His
NP_001182181.2:p.Arg246His
NP_001182183.1:p.Arg264His
NP_001355924.1:p.Arg318His
NP_001355925.1:p.Arg318His
NP_001355926.1:p.Arg318His
NP_001355927.1:p.Arg318His
NP_001355929.1:p.Arg264His
NP_001355930.1:p.Arg264His
NP_001355931.1:p.Arg230His
NP_001355932.1:p.Arg230His
NP_001355933.1:p.Arg230His
NP_001355934.1:p.Arg230His
NP_001357598.1:p.Arg230His
NP_001357599.1:p.Arg230His
NP_001357602.1:p.Arg230His
NP_778243.1:p.Arg318His
NC_000009.11:g.32973572C>T
NR_036577.2:n.904G>A
NR_160920.1:n.792G>A
NR_160921.1:n.923G>A
NR_160922.1:n.1154G>A
NR_160923.1:n.958G>A
NR_160924.1:n.963G>A
NR_160925.1:n.1159G>A
NR_160926.1:n.949G>A
NR_160927.1:n.1042G>A
NR_160928.1:n.968G>A
NR_160929.1:n.846G>A
NR_160930.1:n.899G>A
NR_160931.1:n.1138G>A

Protein change:

R230H

Links:

dbSNP: rs371292546

NCBI 1000 Genomes Browser:

rs371292546

Molecular consequence:

NM_001195251.2:c.*110G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001368999.1:c.*110G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369006.1:c.*110G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_175069.3:c.*110G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001195248.2:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195249.2:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195250.2:c.791G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195252.2:c.737G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195254.2:c.791G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368995.1:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368996.1:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368997.1:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368998.1:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369000.1:c.791G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369001.1:c.791G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369002.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369003.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369004.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369005.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370669.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370670.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370673.1:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_175073.3:c.953G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_036577.2:n.904G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160920.1:n.792G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160921.1:n.923G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160922.1:n.1154G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160923.1:n.958G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160924.1:n.963G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160925.1:n.1159G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160926.1:n.949G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160927.1:n.1042G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160928.1:n.968G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160929.1:n.846G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160930.1:n.899G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160931.1:n.1138G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000340555	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Apr 26, 2016)	germline	clinical testing	Citation Link,
SCV002996601	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000340555

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Apr 26, 2016)

germline

clinical testing

Citation Link,

SCV002996601

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 17, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Eurofins Ntd Llc (ga), SCV000340555.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Invitae, SCV002996601.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 318 of the APTX protein (p.Arg318His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 286950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 1, 2023

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