5-43292887-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_001098272.3(HMGCS1):c.1270G>A(p.Ala424Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,610,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001098272.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HMGCS1 | NM_001098272.3 | c.1270G>A | p.Ala424Thr | missense_variant | Exon 9 of 11 | ENST00000325110.11 | NP_001091742.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HMGCS1 | ENST00000325110.11 | c.1270G>A | p.Ala424Thr | missense_variant | Exon 9 of 11 | 1 | NM_001098272.3 | ENSP00000322706.6 | ||
HMGCS1 | ENST00000433297.2 | c.1270G>A | p.Ala424Thr | missense_variant | Exon 8 of 10 | 5 | ENSP00000399402.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246748Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133208
GnomAD4 exome AF: 0.00000892 AC: 13AN: 1458114Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4AN XY: 725212
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1270G>A (p.A424T) alteration is located in exon 9 (coding exon 7) of the HMGCS1 gene. This alteration results from a G to A substitution at nucleotide position 1270, causing the alanine (A) at amino acid position 424 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at