17-39974377-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178171.5(GSDMA):c.856C>T(p.Leu286Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,596,980 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
GSDMA
NM_178171.5 missense
NM_178171.5 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 2.21
Genes affected
GSDMA (HGNC:13311): (gasdermin A) Predicted to enable phosphatidylinositol-4,5-bisphosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylserine binding activity. Involved in apoptotic process. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSDMA | NM_178171.5 | c.856C>T | p.Leu286Phe | missense_variant | 9/12 | ENST00000301659.9 | |
GSDMA | XM_006721832.4 | c.856C>T | p.Leu286Phe | missense_variant | 9/12 | ||
GSDMA | XM_017024502.3 | c.829C>T | p.Leu277Phe | missense_variant | 8/11 | ||
GSDMA | XM_011524651.4 | c.430C>T | p.Leu144Phe | missense_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSDMA | ENST00000301659.9 | c.856C>T | p.Leu286Phe | missense_variant | 9/12 | 1 | NM_178171.5 | P1 | |
GSDMA | ENST00000635792.1 | c.856C>T | p.Leu286Phe | missense_variant | 9/12 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000415 AC: 6AN: 1444790Hom.: 0 Cov.: 33 AF XY: 0.00000558 AC XY: 4AN XY: 717146
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.856C>T (p.L286F) alteration is located in exon 9 (coding exon 8) of the GSDMA gene. This alteration results from a C to T substitution at nucleotide position 856, causing the leucine (L) at amino acid position 286 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
.;D
REVEL
Benign
Sift
Uncertain
.;D
Sift4G
Pathogenic
.;D
Polyphen
D;D
Vest4
0.53
MVP
0.35
MPC
0.42
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at