rs4795954

chr17-34626239-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001304438.2(TMEM132E):c.180G>A(p.Glu60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,593,570 control chromosomes in the GnomAD database, including 21,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1561 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19868 hom.)
• Consequence: TMEM132E NM_001304438.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.34

Genes affected

TMEM132E (HGNC:26991): (transmembrane protein 132E) Involved in posterior lateral line neuromast hair cell development. Predicted to be located in cell body. Implicated in autosomal recessive nonsyndromic deafness 99. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-34626239-G-A is Benign according to our data. Variant chr17-34626239-G-A is described in ClinVar as [Benign]. Clinvar id is 1277963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E	NM_001304438.2	c.180G>A	p.Glu60=	synonymous_variant	2/9	ENST00000631683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E	ENST00000631683.2	c.180G>A	p.Glu60=	synonymous_variant	2/9	5	NM_001304438.2	P1
TMEM132E	ENST00000321639.7	c.180G>A	p.Glu60=	synonymous_variant	2/10	5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19217 AN: 152104 Hom.: 1562 Cov.: 33

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.169 AC: 35634 AN: 210750 Hom.: 3564 AF XY: 0.174 AC XY: 19907 AN XY: 114658

Gnomad AFR exome AF: 0.0414

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.0892

Gnomad EAS exome AF: 0.370

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.157 AC: 226023 AN: 1441348 Hom.: 19868 Cov.: 34 AF XY: 0.160 AC XY: 114164 AN XY: 715110

Gnomad4 AFR exome AF: 0.0377

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.0902

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.126 AC: 19221 AN: 152222 Hom.: 1561 Cov.: 33 AF XY: 0.132 AC XY: 9802 AN XY: 74420

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0863

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.133

Alfa AF: 0.128 Hom.: 481

Bravo AF: 0.121

Asia WGS AF: 0.281 AC: 974 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	8.0
Dann	Benign	0.96

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: rs4795954; hg19: chr17-32953258; COSMIC: COSV58694445;