2-49918740-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_001330078.2(NRXN1):c.*3204C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 152,086 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 (★).
Frequency
Consequence
NM_001330078.2 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669 | c.*3204C>T | 3_prime_UTR_variant | Exon 23 of 23 | 5 | NM_001330078.2 | ENSP00000385017.2 | |||
NRXN1 | ENST00000625672 | c.*3204C>T | 3_prime_UTR_variant | Exon 21 of 21 | 1 | ENSP00000485887.1 | ||||
NRXN1 | ENST00000406316 | c.*3204C>T | 3_prime_UTR_variant | Exon 22 of 22 | 5 | ENSP00000384311.2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152086Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 0
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74290
ClinVar
Submissions by phenotype
Pitt-Hopkins-like syndrome 2 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at