rs200332295
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001330078.2(NRXN1):c.1679C>A(p.Thr560Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,500 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. T560A) 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.1679C>A | p.Thr560Asn | missense_variant | 9/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.1679C>A | p.Thr560Asn | missense_variant | 9/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249266Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135222
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461500Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727030
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2022 | The c.1799C>A (p.T600N) alteration is located in exon 10 (coding exon 9) of the NRXN1 gene. This alteration results from a C to A substitution at nucleotide position 1799, causing the threonine (T) at amino acid position 600 to be replaced by an asparagine (N). 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 | May 27, 2023 | 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: 472639). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is present in population databases (rs200332295, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 600 of the NRXN1 protein (p.Thr600Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at