rs374385878
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_004318.4(ASPH):c.2203C>T(p.Arg735Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,612,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_004318.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPH | ENST00000379454.9 | c.2203C>T | p.Arg735Trp | missense_variant | Exon 25 of 25 | 1 | NM_004318.4 | ENSP00000368767.4 | ||
ASPH | ENST00000541428.5 | c.2116C>T | p.Arg706Trp | missense_variant | Exon 25 of 25 | 2 | ENSP00000437864.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000243 AC: 6AN: 247216 AF XY: 0.0000149 show subpopulations
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1460614Hom.: 0 Cov.: 29 AF XY: 0.0000193 AC XY: 14AN XY: 726610 show subpopulations
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74464 show subpopulations
ClinVar
Submissions by phenotype
Thoracic aortic aneurysm or dissection Pathogenic:1
- -
Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at