rs368106957
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_030665.4(RAI1):c.4693G>A(p.Val1565Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V1565L) has been classified as Uncertain significance.
Frequency
Consequence
NM_030665.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.4693G>A | p.Val1565Met | missense_variant | 3/6 | ENST00000353383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.4693G>A | p.Val1565Met | missense_variant | 3/6 | 1 | NM_030665.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000207 AC: 52AN: 250996Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135776
GnomAD4 exome AF: 0.000146 AC: 213AN: 1461536Hom.: 0 Cov.: 36 AF XY: 0.000175 AC XY: 127AN XY: 727060
GnomAD4 genome AF: 0.000158 AC: 24AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 09, 2020 | This variant is associated with the following publications: (PMID: 29458409) - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Oct 13, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 13, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 26, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
RAI1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 04, 2020 | This variant is classified as likely 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