rs1430859209
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001330078.2(NRXN1):c.1135-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 1,562,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001330078.2 splice_region, splice_polypyrimidine_tract, intron
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.1135-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000401669.7 | |||
LOC101927089 | XR_245002.5 | n.88+246G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.1135-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001330078.2 | A1 | |||
ENST00000634985.1 | n.49+246G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180370Hom.: 0 AF XY: 0.0000210 AC XY: 2AN XY: 95240
GnomAD4 exome AF: 0.00000284 AC: 4AN: 1410526Hom.: 0 Cov.: 28 AF XY: 0.00000287 AC XY: 2AN XY: 697482
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge - |
Pitt-Hopkins-like syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at