3-158122299-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001271838.2(RSRC1):c.194+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000215 in 1,396,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001271838.2 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000215 AC: 3AN: 1396234Hom.: 0 Cov.: 25 AF XY: 0.00000288 AC XY: 2AN XY: 694634
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
The c.194+1G>A intronic alteration results from a G to A substitution one nucleotide after exon 2 (coding exon 1) of the RSRC1 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the RSRC1 c.194+1G>A alteration was not observed, with coverage at this position; however this position was flagged as low confidence. The c.194+1G nucleotide is conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. Based on the available evidence, this alteration is classified as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at