17-39974377-C-T

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

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21
Variant links:
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]

Genome browser will be placed here

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
GSDMANM_178171.5 linkuse as main transcriptc.856C>T p.Leu286Phe missense_variant 9/12 ENST00000301659.9
GSDMAXM_006721832.4 linkuse as main transcriptc.856C>T p.Leu286Phe missense_variant 9/12
GSDMAXM_017024502.3 linkuse as main transcriptc.829C>T p.Leu277Phe missense_variant 8/11
GSDMAXM_011524651.4 linkuse as main transcriptc.430C>T p.Leu144Phe missense_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSDMAENST00000301659.9 linkuse as main transcriptc.856C>T p.Leu286Phe missense_variant 9/121 NM_178171.5 P1
GSDMAENST00000635792.1 linkuse as main transcriptc.856C>T p.Leu286Phe missense_variant 9/125 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000415
AC:
6
AN:
1444790
Hom.:
0
Cov.:
33
AF XY:
0.00000558
AC XY:
4
AN XY:
717146
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000240
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.0000334
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.00000829
AC:
1

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 submitterclinical testingAmbry GeneticsDec 19, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.025
T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.73
.;T
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.2
M;M
MutationTaster
Benign
0.55
D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.2
.;D
REVEL
Benign
0.24
Sift
Uncertain
0.011
.;D
Sift4G
Pathogenic
0.0
.;D
Polyphen
1.0
D;D
Vest4
0.53
MVP
0.35
MPC
0.42
ClinPred
0.98
D
GERP RS
4.9
Varity_R
0.28
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369000767; hg19: chr17-38130630; API