8-143561418-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024736.7(GSDMD):c.731C>T(p.Ala244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,611,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024736.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSDMD | NM_024736.7 | c.731C>T | p.Ala244Val | missense_variant | 6/11 | ENST00000262580.9 | |
GSDMD | NM_001166237.1 | c.731C>T | p.Ala244Val | missense_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSDMD | ENST00000262580.9 | c.731C>T | p.Ala244Val | missense_variant | 6/11 | 1 | NM_024736.7 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246446Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133876
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1459082Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 725698
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74280
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.731C>T (p.A244V) alteration is located in exon 9 (coding exon 5) of the GSDMD gene. This alteration results from a C to T substitution at nucleotide position 731, causing the alanine (A) at amino acid position 244 to be replaced by a valine (V). 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