Variant chr17-39970544-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178171.5(GSDMA):c.455T>A(p.Val152Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,330 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

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GSDMA
NM_178171.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSDMA	NM_178171.5 linkuse as main transcript	c.455T>A	p.Val152Glu	missense_variant	4/12	ENST00000301659.9
GSDMA	XM_006721832.4 linkuse as main transcript	c.455T>A	p.Val152Glu	missense_variant	4/12
GSDMA	XM_017024502.3 linkuse as main transcript	c.455T>A	p.Val152Glu	missense_variant	4/11
GSDMA	XM_011524651.4 linkuse as main transcript	c.29T>A	p.Val10Glu	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GSDMA	ENST00000301659.9 linkuse as main transcript	c.455T>A	p.Val152Glu	missense_variant	4/12	1	NM_178171.5	P1
GSDMA	ENST00000635792.1 linkuse as main transcript	c.455T>A	p.Val152Glu	missense_variant	4/12	5		P1
GSDMA	ENST00000577447.1 linkuse as main transcript	c.455T>A	p.Val152Glu	missense_variant	4/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456330

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Oct 30, 2023

The c.455T>A (p.V152E) alteration is located in exon 4 (coding exon 3) of the GSDMA gene. This alteration results from a T to A substitution at nucleotide position 455, causing the valine (V) at amino acid position 152 to be replaced by a glutamic acid (E). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Benign

0.94

DEOGEN2

Benign

0.20

T;T;T

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.034

MetaRNN

Pathogenic

0.90

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.8

M;M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

Polyphen

1.0

D;D;.

Vest4

0.92

MutPred

0.83

Gain of disorder (P = 0.0202);Gain of disorder (P = 0.0202);Gain of disorder (P = 0.0202);

MVP

0.47

MPC

0.49

ClinPred

0.99

GERP RS

5.6

Varity_R

0.88

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: 1

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over