rs4795954

Variant names:

• chr17-34626239-G-A
• rs4795954
• NM_001304438.2:c.180G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001304438.2(TMEM132E):​c.180G>A​(p.Glu60Glu) 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:3
• Conservation: PhyloP100: 3.34
• Publications: 12 publications found

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]

TMEM132E Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 99

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TMEM132E	NM_001304438.2	c.180G>A	p.Glu60Glu	synonymous_variant	Exon 2 of 9	ENST00000631683.2	NP_001291367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132E	ENST00000631683.2	c.180G>A	p.Glu60Glu	synonymous_variant	Exon 2 of 9	5	NM_001304438.2	ENSP00000487800.2
TMEM132E	ENST00000321639.7	c.180G>A	p.Glu60Glu	synonymous_variant	Exon 2 of 10	5		ENSP00000316532.5

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

GnomAD2 exomes AF: 0.169 AC: 35634 AN: 210750 AF XY: 0.174

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 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

African (AFR) AF: 0.0377 AC: 1250 AN: 33190

American (AMR) AF: 0.167 AC: 7027 AN: 42024

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 2318 AN: 25686

East Asian (EAS) AF: 0.376 AC: 14517 AN: 38614

South Asian (SAS) AF: 0.262 AC: 21796 AN: 83252

European-Finnish (FIN) AF: 0.153 AC: 7778 AN: 50756

Middle Eastern (MID) AF: 0.127 AC: 702 AN: 5538

European-Non Finnish (NFE) AF: 0.146 AC: 161219 AN: 1102770

Other (OTH) AF: 0.158 AC: 9416 AN: 59518

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

African (AFR) AF: 0.0447 AC: 1858 AN: 41582

American (AMR) AF: 0.142 AC: 2180 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0863 AC: 299 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1876 AN: 5150

South Asian (SAS) AF: 0.266 AC: 1284 AN: 4826

European-Finnish (FIN) AF: 0.163 AC: 1730 AN: 10608

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9498 AN: 67974

Other (OTH) AF: 0.133 AC: 280 AN: 2110

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.0
DANN	Benign	0.96
PhyloP100		3.3
Mutation Taster		=99/1	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: rs4795954; hg19: chr17-32953258; COSMIC: COSV58694445;