chr17-39972395-C-T

Variant names:

• chr17-39972395-C-T
• rs3859192
• NM_178171.5:c.704-192C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 83 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	NM_178171.5	MANE Select	c.704-192C>T		intron	N/A	NP_835465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.704-192C>T		intron	N/A	ENSP00000301659.4
	GSDMA	ENST00000635792.1	TSL:5	c.704-192C>T		intron	N/A	ENSP00000490739.1

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

African (AFR) AF: 0.332 AC: 13773 AN: 41432

American (AMR) AF: 0.396 AC: 6042 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2577 AN: 5168

South Asian (SAS) AF: 0.286 AC: 1380 AN: 4818

European-Finnish (FIN) AF: 0.444 AC: 4669 AN: 10508

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31956 AN: 67954

Other (OTH) AF: 0.398 AC: 839 AN: 2110

Alfa AF: 0.447 Hom.: 66664

Bravo AF: 0.411

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.78
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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