rs756926807
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001164507.2(NEB):āc.6119A>Gā(p.Tyr2040Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000577 in 1,610,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Y2040Y) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.6119A>G | p.Tyr2040Cys | missense_variant | 48/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.6119A>G | p.Tyr2040Cys | missense_variant | 48/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.6119A>G | p.Tyr2040Cys | missense_variant | 48/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.6119A>G | p.Tyr2040Cys | missense_variant | 48/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.6119A>G | p.Tyr2040Cys | missense_variant | 48/150 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000187 AC: 46AN: 245370Hom.: 1 AF XY: 0.000211 AC XY: 28AN XY: 133004
GnomAD4 exome AF: 0.0000583 AC: 85AN: 1458342Hom.: 0 Cov.: 30 AF XY: 0.0000731 AC XY: 53AN XY: 725250
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74368
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 01, 2024 | Variant summary: NEB c.6119A>G (p.Tyr2040Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 245370 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in NEB causing Nemaline Myopathy 2 (0.00019 vs 0.0035), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.6119A>G in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 570192). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 25, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at