3-52204896-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000688.6(ALAS1):c.781C>T(p.Arg261Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,846 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 Uncertain significance (★).
Frequency
Consequence
NM_000688.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALAS1 | ENST00000484952.6 | c.781C>T | p.Arg261Trp | missense_variant | Exon 6 of 12 | 1 | NM_000688.6 | ENSP00000418779.1 | ||
ALAS1 | ENST00000310271.6 | c.781C>T | p.Arg261Trp | missense_variant | Exon 5 of 11 | 1 | ENSP00000309259.2 | |||
ALAS1 | ENST00000469224.5 | c.781C>T | p.Arg261Trp | missense_variant | Exon 5 of 11 | 1 | ENSP00000417719.1 | |||
ALAS1 | ENST00000394965.6 | c.781C>T | p.Arg261Trp | missense_variant | Exon 6 of 12 | 2 | ENSP00000378416.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251104Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135724
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461712Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727178
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74300
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.781C>T (p.R261W) alteration is located in exon 6 (coding exon 4) of the ALAS1 gene. This alteration results from a C to T substitution at nucleotide position 781, causing the arginine (R) at amino acid position 261 to be replaced by a tryptophan (W). 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