rs202234374
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001164507.2(NEB):c.5696C>T(p.Thr1899Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,613,756 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. T1899N) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.5696C>T | p.Thr1899Ile | missense_variant | 45/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.5696C>T | p.Thr1899Ile | missense_variant | 45/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.5696C>T | p.Thr1899Ile | missense_variant | 45/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.5696C>T | p.Thr1899Ile | missense_variant | 45/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.5696C>T | p.Thr1899Ile | missense_variant | 45/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000478 AC: 119AN: 248838Hom.: 0 AF XY: 0.000341 AC XY: 46AN XY: 135002
GnomAD4 exome AF: 0.000145 AC: 212AN: 1461472Hom.: 1 Cov.: 31 AF XY: 0.000125 AC XY: 91AN XY: 727022
GnomAD4 genome ? AF: 0.000282 AC: 43AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74460
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2Benign:1
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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 26, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Oct 06, 2017 | BP1,BP4; This alteration is a missense alteration in a gene for which primarily truncating variants are known to cause disease, and is predicted to be tolerated by multiple functional prediction tools. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at