chr21-14964958-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_003489.4(NRIP1):c.3235G>T(p.Val1079Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,613,840 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_003489.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRIP1 | NM_003489.4 | c.3235G>T | p.Val1079Phe | missense_variant | 4/4 | ENST00000318948.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRIP1 | ENST00000318948.7 | c.3235G>T | p.Val1079Phe | missense_variant | 4/4 | 2 | NM_003489.4 | P1 | |
NRIP1 | ENST00000400199.5 | c.3235G>T | p.Val1079Phe | missense_variant | 3/3 | 3 | P1 | ||
NRIP1 | ENST00000400202.5 | c.3235G>T | p.Val1079Phe | missense_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000401 AC: 61AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000422 AC: 106AN: 251090Hom.: 1 AF XY: 0.000464 AC XY: 63AN XY: 135708
GnomAD4 exome AF: 0.000649 AC: 948AN: 1461652Hom.: 4 Cov.: 33 AF XY: 0.000695 AC XY: 505AN XY: 727122
GnomAD4 genome ? AF: 0.000401 AC: 61AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 28AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2023 | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1079 of the NRIP1 protein (p.Val1079Phe). This variant is present in population databases (rs140803495, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with NRIP1-related conditions. - |
NRIP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 05, 2023 | 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