17-34581045-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001304438.2(TMEM132E):c.-32T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,522,808 control chromosomes in the GnomAD database, including 557,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60087 hom., cov: 35)
  • Exomes 𝑓: 0.85 (497538 hom.)
• Consequence: TMEM132E NM_001304438.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.375

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 17-34581045-T-C is Benign according to our data. Variant chr17-34581045-T-C is described in ClinVar as [Benign]. Clinvar id is 1235963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E	NM_001304438.2	c.-32T>C		5_prime_UTR_variant	1/9	ENST00000631683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E	ENST00000631683.2	c.-32T>C		5_prime_UTR_variant	1/9	5	NM_001304438.2	P1
TMEM132E	ENST00000321639.7	c.-32T>C		5_prime_UTR_variant	1/10	5

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134845 AN: 152166 Hom.: 60022 Cov.: 35

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.866

GnomAD3 exomes AF: 0.835 AC: 132298 AN: 158516 Hom.: 55513 AF XY: 0.832 AC XY: 74185 AN XY: 89170

Gnomad AFR exome AF: 0.972

Gnomad AMR exome AF: 0.812

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.830

Gnomad SAS exome AF: 0.763

Gnomad FIN exome AF: 0.904

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.851 AC: 1166691 AN: 1370526 Hom.: 497538 Cov.: 28 AF XY: 0.849 AC XY: 576167 AN XY: 678706

Gnomad4 AFR exome AF: 0.976

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.826

Gnomad4 EAS exome AF: 0.889

Gnomad4 SAS exome AF: 0.783

Gnomad4 FIN exome AF: 0.908

Gnomad4 NFE exome AF: 0.852

Gnomad4 OTH exome AF: 0.846

GnomAD4 genome AF: 0.886 AC: 134970 AN: 152282 Hom.: 60087 Cov.: 35 AF XY: 0.887 AC XY: 66040 AN XY: 74458

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.868

Alfa AF: 0.863 Hom.: 11548

Bravo AF: 0.883

Asia WGS AF: 0.807 AC: 2800 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Hearing loss, autosomal recessive 99 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	15
Dann	Benign	0.80

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: rs4795938; hg19: chr17-32908064;