rs201886728
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001164507.2(NEB):c.18862G>A(p.Val6288Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000777 in 1,581,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V6288F) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.18862G>A | p.Val6288Ile | missense_variant | 120/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.18862G>A | p.Val6288Ile | missense_variant | 120/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.18862G>A | p.Val6288Ile | missense_variant | 120/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.18862G>A | p.Val6288Ile | missense_variant | 120/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000638 AC: 97AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000373 AC: 91AN: 244090Hom.: 0 AF XY: 0.000340 AC XY: 45AN XY: 132246
GnomAD4 exome AF: 0.000791 AC: 1131AN: 1429132Hom.: 0 Cov.: 30 AF XY: 0.000759 AC XY: 535AN XY: 705228
GnomAD4 genome ? AF: 0.000637 AC: 97AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41AN XY: 74380
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter 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) | Feb 09, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 04, 2023 | - - |
Nemaline myopathy 2 Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 30, 2024 | The c.13759G>A (p.V4587I) alteration is located in exon 93 (coding exon 91) of the NEB gene. This alteration results from a G to A substitution at nucleotide position 13759, causing the valine (V) at amino acid position 4587 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Nemaline myopathy 2;C5543431:Arthrogryposis multiplex congenita 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 26, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at