rs1060503176
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001330078.2(NRXN1):c.1786A>T(p.Thr596Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T596I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330078.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRXN1 | NM_001330078.2 | c.1786A>T | p.Thr596Ser | missense_variant | 10/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.1786A>T | p.Thr596Ser | missense_variant | 10/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151910Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151910Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74174
ClinVar
Submissions by phenotype
Pitt-Hopkins-like syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 01, 2016 | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NRXN1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces threonine with serine at codon 636 of the NRXN1 protein (p.Thr636Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at