rs762326241
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001330078.2(NRXN1):c.2008C>T(p.Pro670Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,694 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. P670A) 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.2008C>T | p.Pro670Ser | missense_variant | 10/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.2008C>T | p.Pro670Ser | missense_variant | 10/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249346Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135260
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727126
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2021 | The c.2128C>T (p.P710S) alteration is located in exon 11 (coding exon 10) of the NRXN1 gene. This alteration results from a C to T substitution at nucleotide position 2128, causing the proline (P) at amino acid position 710 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Pitt-Hopkins-like syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2023 | This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 2233747). This variant is present in population databases (rs762326241, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 710 of the NRXN1 protein (p.Pro710Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at