rs62001869
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_016616.5(NME8):c.1007G>A(p.Arg336His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,582,892 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R336C) has been classified as Uncertain significance.
Frequency
Consequence
NM_016616.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NME8 | NM_016616.5 | c.1007G>A | p.Arg336His | missense_variant | 13/18 | ENST00000199447.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NME8 | ENST00000199447.9 | c.1007G>A | p.Arg336His | missense_variant | 13/18 | 1 | NM_016616.5 | P1 | |
NME8 | ENST00000440017.5 | c.1007G>A | p.Arg336His | missense_variant | 12/16 | 1 | P1 | ||
NME8 | ENST00000426106.1 | c.118G>A | p.Val40Ile | missense_variant, NMD_transcript_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0248 AC: 3771AN: 151944Hom.: 78 Cov.: 33
GnomAD3 exomes AF: 0.0143 AC: 3571AN: 250530Hom.: 43 AF XY: 0.0130 AC XY: 1762AN XY: 135416
GnomAD4 exome AF: 0.0138 AC: 19748AN: 1430830Hom.: 179 Cov.: 27 AF XY: 0.0136 AC XY: 9680AN XY: 713818
GnomAD4 genome ? AF: 0.0248 AC: 3774AN: 152062Hom.: 79 Cov.: 33 AF XY: 0.0243 AC XY: 1804AN XY: 74314
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Arg336His in exon 13 of TXNDC3: This variant is not expected to have clinical si gnificance because it has been identified in 4.4% (196/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs62001869). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia 6 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 06, 2023 | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2019 | This variant is associated with the following publications: (PMID: 29177109) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at