ENST00000479636.1:n.2004A>G

Variant names:

• chr7-24704034-T-C
• rs10486430
• ENST00000479636.1:n.2004A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000479636.1(GSDME):​n.2004A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 152,262 control chromosomes in the GnomAD database, including 156 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 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSDME ENST00000479636.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 2 publications found

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]

GSDME Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal dominant nonsyndromic hearing loss 5

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479636.1. 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
	GSDME	NM_001127453.2	MANE Select	c.1184-1201A>G		intron	N/A	NP_001120925.1
	GSDME	NM_004403.3		c.1184-1201A>G		intron	N/A	NP_004394.1
	GSDME	NM_001127454.2		c.692-1201A>G		intron	N/A	NP_001120926.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDME	ENST00000479636.1	TSL:1	n.2004A>G		non_coding_transcript_exon	Exon 1 of 2
	GSDME	ENST00000645220.1	MANE Select	c.1184-1201A>G		intron	N/A	ENSP00000494186.1
	GSDME	ENST00000342947.9	TSL:1	c.1184-1201A>G		intron	N/A	ENSP00000339587.3

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5852 AN: 152144 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.00946

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0392

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0384 AC: 5853 AN: 152262 Hom.: 156 Cov.: 32 AF XY: 0.0374 AC XY: 2783 AN XY: 74446

African (AFR) AF: 0.00951 AC: 395 AN: 41550

American (AMR) AF: 0.0319 AC: 488 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4824

European-Finnish (FIN) AF: 0.0577 AC: 612 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3871 AN: 68026

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0537 Hom.: 117

Bravo AF: 0.0359

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.072
DANN	Benign	0.49
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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: rs10486430; hg19: chr7-24743653;