NM_006172.4(NPPA):c.279T>G (p.Asp93Glu) AND Atrial fibrillation, familial, 6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 29, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003631128.2

Allele description [Variation Report for NM_006172.4(NPPA):c.279T>G (p.Asp93Glu)]

NM_006172.4(NPPA):c.279T>G (p.Asp93Glu)

Genes:

NPPA-AS1:NPPA antisense RNA 1 [Gene - HGNC]
LOC114827827:VISTA enhancer hs2123 [Gene]
NPPA:natriuretic peptide A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_006172.4(NPPA):c.279T>G (p.Asp93Glu)

HGVS:

NC_000001.11:g.11847284A>C
NG_012926.1:g.5500T>G
NG_065183.1:g.566A>C
NM_006172.4:c.279T>GMANE SELECT
NP_006163.1:p.Asp93Glu
LRG_751t1:c.279T>G
LRG_751:g.5500T>G
NC_000001.10:g.11907341A>C
NM_006172.3:c.279T>G

Protein change:

D93E

Links:

dbSNP: rs148193368

NCBI 1000 Genomes Browser:

rs148193368

Molecular consequence:

NM_006172.4:c.279T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrial fibrillation, familial, 6 (ATFB6)
Identifiers:: MONDO: MONDO:0012816; MedGen: C2677294; OMIM: 612201

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004397661	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24144883, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004397661

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation.

Olesen MS, Andreasen L, Jabbari J, Refsgaard L, Haunsø S, Olesen SP, Nielsen JB, Schmitt N, Svendsen JH.

Heart Rhythm. 2014 Feb;11(2):246-51. doi: 10.1016/j.hrthm.2013.10.034. Epub 2013 Oct 18.

PubMed [citation]

PMID:: 24144883

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004397661.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 449329). This missense change has been observed in individual(s) with atrial fibrillation (PMID: 24144883). This variant is present in population databases (rs148193368, gnomAD 0.04%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 93 of the NPPA protein (p.Asp93Glu).

#	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: Sep 29, 2024

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