Variant chr17-39974311-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178171.5(GSDMA):c.790G>C(p.Val264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GSDMA
NM_178171.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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]

GSDMA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2924237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMA	NM_178171.5 linkuse as main transcript	c.790G>C	p.Val264Leu	missense_variant	9/12	ENST00000301659.9	NP_835465.2	Q96QA5
GSDMA	XM_006721832.4 linkuse as main transcript	c.790G>C	p.Val264Leu	missense_variant	9/12		XP_006721895.1	Q96QA5
GSDMA	XM_017024502.3 linkuse as main transcript	c.763G>C	p.Val255Leu	missense_variant	8/11		XP_016879991.1
GSDMA	XM_011524651.4 linkuse as main transcript	c.364G>C	p.Val122Leu	missense_variant	7/10		XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9 linkuse as main transcript	c.790G>C	p.Val264Leu	missense_variant	9/12	1	NM_178171.5	ENSP00000301659.4		Q96QA5
GSDMA	ENST00000635792.1 linkuse as main transcript	c.790G>C	p.Val264Leu	missense_variant	9/12	5		ENSP00000490739.1		Q96QA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244022

Hom.:

AF XY:

0.00000756

AC XY:

AN XY:

132318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459078

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Sep 12, 2023

The c.790G>C (p.V264L) alteration is located in exon 9 (coding exon 8) of the GSDMA gene. This alteration results from a G to C substitution at nucleotide position 790, causing the valine (V) at amino acid position 264 to be replaced by a leucine (L). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

T;T

Eigen

Benign

0.066

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

.;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.48

P;P

Vest4

0.45

MutPred

0.68

Loss of methylation at K261 (P = 0.0823);Loss of methylation at K261 (P = 0.0823);

MVP

0.13

MPC

0.19

ClinPred

0.96

GERP RS

2.6

Varity_R

0.54

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over