17-39954436-T-G

Position:

• chr17-39954436-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635792.1(GSDMA):​c.-6+1131T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,078 control chromosomes in the GnomAD database, including 36,136 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (36136 hom., cov: 32)
• Consequence: GSDMA ENST00000635792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000635792.1	c.-6+1131T>G		intron_variant		5		ENSP00000490739	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104056 AN: 151960 Hom.: 36106 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.685 AC: 104139 AN: 152078 Hom.: 36136 Cov.: 32 AF XY: 0.688 AC XY: 51152 AN XY: 74322

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.642

Alfa AF: 0.627 Hom.: 21306

Bravo AF: 0.692

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17609240; hg19: chr17-38110689;