rs200239095
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001164507.2(NEB):c.20032C>T(p.Arg6678Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000407 in 1,597,844 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6678H) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.20032C>T | p.Arg6678Cys | missense_variant | 130/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.20032C>T | p.Arg6678Cys | missense_variant | 130/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.20032C>T | p.Arg6678Cys | missense_variant | 130/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.20032C>T | p.Arg6678Cys | missense_variant | 130/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152112Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000813 AC: 185AN: 227490Hom.: 2 AF XY: 0.000851 AC XY: 104AN XY: 122258
GnomAD4 exome AF: 0.000401 AC: 580AN: 1445732Hom.: 4 Cov.: 30 AF XY: 0.000427 AC XY: 306AN XY: 717466
GnomAD4 genome ? AF: 0.000467 AC: 71AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31AN XY: 74304
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 26, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 20, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | NEB: BP4, BS2 - |
NEB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 10, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at