rs10486429

chr7-24703859-G-A

Variant summary

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

The NM_001127453.2(GSDME):c.1184-1026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,336 control chromosomes in the GnomAD database, including 158 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 0.038 (158 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: GSDME NM_001127453.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

Genes affected

GSDME (HGNC:2810): (gasdermin E) Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDME	NM_001127453.2	c.1184-1026C>T		intron_variant		ENST00000645220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDME	ENST00000645220.1	c.1184-1026C>T		intron_variant			NM_001127453.2	P1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5861 AN: 152182 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.00951

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.0556 AC: 2 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.0667 AC XY: 2 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0385 AC: 5862 AN: 152300 Hom.: 158 Cov.: 32 AF XY: 0.0374 AC XY: 2786 AN XY: 74464

Gnomad4 AFR AF: 0.00955

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0538 Hom.: 104

Bravo AF: 0.0359

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.98
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10486429; hg19: chr7-24743478;