chr17-19648972-A-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_001369148.2(ALDH3A2):c.-688A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,148 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 (★★).
Frequency
Consequence
NM_001369148.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1434148Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1AN XY: 710836
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Sjögren-Larsson syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 19, 2023 | Variant summary: ALDH3A2 c.1A>T (p.Met1?, aka p.Met1Leu) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The first potential downstream in-frame start codon (ATG) is located in the same exon, at Met33. Several other start-lost variants, and truncations upstream from Met33 have been reported in individuals affected with Sjogren-Larsson Syndrome (HGMD). The variant was absent in 201014 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1A>T in individuals affected with Sjogren-Larsson Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 02, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.