chr2-45546732-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_018079.5(SRBD1):c.1874G>A(p.Cys625Tyr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_018079.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRBD1 | NM_018079.5 | c.1874G>A | p.Cys625Tyr | missense_variant, splice_region_variant | 14/21 | ENST00000263736.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRBD1 | ENST00000263736.5 | c.1874G>A | p.Cys625Tyr | missense_variant, splice_region_variant | 14/21 | 2 | NM_018079.5 | P1 | |
SRBD1 | ENST00000475073.5 | n.281G>A | splice_region_variant, non_coding_transcript_exon_variant | 3/6 | 4 | ||||
SRBD1 | ENST00000493649.1 | n.655G>A | non_coding_transcript_exon_variant | 6/6 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461448Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727048
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.1874G>A (p.C625Y) alteration is located in exon 15 (coding exon 14) of the SRBD1 gene. This alteration results from a G to A substitution at nucleotide position 1874, causing the cysteine (C) at amino acid position 625 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at