rs199561088
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001330078.2(NRXN1):c.637G>T(p.Gly213Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,597,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. G213R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330078.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRXN1 | NM_001330078.2 | c.637G>T | p.Gly213Trp | missense_variant | 2/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.637G>T | p.Gly213Trp | missense_variant | 2/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000231 AC: 5AN: 216108Hom.: 0 AF XY: 0.0000339 AC XY: 4AN XY: 118060
GnomAD4 exome AF: 0.00000900 AC: 13AN: 1444910Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 10AN XY: 717298
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
Pitt-Hopkins-like syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2023 | This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 213 of the NRXN1 protein (p.Gly213Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at