chr13-113122926-G-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000504.4(F10):c.70+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.0000149 in 1,609,256 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 Likely pathogenic (no stars).
Frequency
Consequence
NM_000504.4 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
F10 | NM_000504.4 | c.70+1G>A | splice_donor_variant, intron_variant | Intron 1 of 7 | ENST00000375559.8 | NP_000495.1 | ||
F10 | NM_001312674.2 | c.70+1G>A | splice_donor_variant, intron_variant | Intron 1 of 6 | NP_001299603.1 | |||
F10 | NM_001312675.2 | c.70+1G>A | splice_donor_variant, intron_variant | Intron 1 of 7 | NP_001299604.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152264Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245842Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133770
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1456992Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 724994
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74388
ClinVar
Submissions by phenotype
F10-related disorder Pathogenic:1
The F10 c.70+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in the compound heterozygous state in an individual with Factor X deficiency (Wang et al. 2004. PubMed ID: 15569527). This variant is reported in 0.0081% of alleles in individuals of African descent in gnomAD. Variants that disrupt the consensus splice donor site in F10 are expected to be pathogenic. This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at