rs375412223
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):āc.5939T>Cā(p.Leu1980Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,378 control chromosomes in the GnomAD database, including 1 homozygotes. 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. L1980F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.5939T>C | p.Leu1980Ser | missense_variant | 46/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.5939T>C | p.Leu1980Ser | missense_variant | 46/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.5939T>C | p.Leu1980Ser | missense_variant | 46/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.5939T>C | p.Leu1980Ser | missense_variant | 46/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.5939T>C | p.Leu1980Ser | missense_variant | 46/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000257 AC: 64AN: 248694Hom.: 0 AF XY: 0.000319 AC XY: 43AN XY: 134900
GnomAD4 exome AF: 0.000152 AC: 222AN: 1461070Hom.: 1 Cov.: 31 AF XY: 0.000209 AC XY: 152AN XY: 726804
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74470
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:3Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 18, 2019 | - - |
Nemaline myopathy 2;C5543431:Arthrogryposis multiplex congenita 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 13, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at