chr17-19741197-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000691.5(ALDH3A1):c.703G>A(p.Gly235Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Consequence
NM_000691.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251414Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135868
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461598Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727102
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
Keratoconus Pathogenic:1
ALDH3A1 is thought to be involved in KC etiology.12-14 ALDH3A1 variants, rs1042183 and rs2228100, are strongly associated with KC in the Polish and Korean populations.12, 14 The association of ALDH3A1 with intraocular pressure15 and refractive astigmatism16, 17 have also been observed. Furthermore, the relationship between astigmatism and KC has been reported, as 14.1% of patients with more than 2D astigmatism suffer from KC.18 Our findings further demonstrated the association of ALDH3A1 with KC. A novel SNP in ALDH3A1 was detected, g.19644510G>A, (c.703G>A, p.Gly235Arg [rs761232139]), causing a p.G235R amino acid change. This variant is located in exon 6 of ALDH3A1 gene and is predicted as highly conserved among species and probably damaging. The variant was identified in all KC members from the family 2, which means that rs761232139 may be a risk factor for KC and inherited in a dominant model. The residue was considered as a distinct structural and/or functional sequence of ALDH3A1, which is adjacent to the active site Cys-243. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at