chr17-39972395-C-T

Position:

• chr17-39972395-C-T

Variant summary

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

The NM_178171.5(GSDMA):​c.704-192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,928 control chromosomes in the GnomAD database, including 13,488 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 0.42 (13488 hom., cov: 32)
• Consequence: GSDMA NM_178171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMA	NM_178171.5	c.704-192C>T		intron_variant		ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.704-192C>T		intron_variant			XP_006721895.1
GSDMA	XM_011524651.4	c.278-192C>T		intron_variant			XP_011522953.1
GSDMA	XM_017024502.3	c.703+219C>T		intron_variant			XP_016879991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9	c.704-192C>T		intron_variant		1	NM_178171.5	ENSP00000301659	P1
GSDMA	ENST00000635792.1	c.704-192C>T		intron_variant		5		ENSP00000490739	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63140 AN: 151810 Hom.: 13479 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.416 AC: 63182 AN: 151928 Hom.: 13488 Cov.: 32 AF XY: 0.411 AC XY: 30538 AN XY: 74252

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.398

Alfa AF: 0.447 Hom.: 33475

Bravo AF: 0.411

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs3859192; hg19: chr17-38128648; COSMIC: COSV56975457; COSMIC: COSV56975457;