rs78540316
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001330078.2(NRXN1):c.1285C>T(p.Pro429Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,609,946 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P429L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330078.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRXN1 | NM_001330078.2 | c.1285C>T | p.Pro429Ser | missense_variant | 8/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.1285C>T | p.Pro429Ser | missense_variant | 8/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00312 AC: 475AN: 152128Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00373 AC: 915AN: 245262Hom.: 5 AF XY: 0.00362 AC XY: 482AN XY: 133070
GnomAD4 exome AF: 0.00343 AC: 5004AN: 1457700Hom.: 24 Cov.: 30 AF XY: 0.00335 AC XY: 2426AN XY: 725086
GnomAD4 genome AF: 0.00312 AC: 475AN: 152246Hom.: 1 Cov.: 32 AF XY: 0.00349 AC XY: 260AN XY: 74434
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 11, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 17, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | NRXN1: BS2 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 14, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 18, 2018 | - - |
Pitt-Hopkins-like syndrome 2 Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Jul 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 20, 2018 | 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. - |
NRXN1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 06, 2019 | This variant is classified as 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