17-34580843-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001304438.2(TMEM132E):c.-234G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 455,300 control chromosomes in the GnomAD database, including 3,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (908 hom., cov: 34)
  • Exomes 𝑓: 0.10 (2286 hom.)
• Consequence: TMEM132E NM_001304438.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 17-34580843-G-A is Benign according to our data. Variant chr17-34580843-G-A is described in ClinVar as [Benign]. Clinvar id is 1222603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E	NM_001304438.2	c.-234G>A		5_prime_UTR_variant	1/9	ENST00000631683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E	ENST00000631683.2	c.-234G>A		5_prime_UTR_variant	1/9	5	NM_001304438.2	P1
TMEM132E	ENST00000321639.7	c.-234G>A		5_prime_UTR_variant	1/10	5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15377 AN: 152082 Hom.: 905 Cov.: 34

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.103 AC: 31082 AN: 303100 Hom.: 2286 Cov.: 0 AF XY: 0.105 AC XY: 16635 AN XY: 157700

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.0895

Gnomad4 NFE exome AF: 0.0738

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.101 AC: 15399 AN: 152200 Hom.: 908 Cov.: 34 AF XY: 0.106 AC XY: 7872 AN XY: 74416

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0882 Hom.: 92

Bravo AF: 0.102

Asia WGS AF: 0.241 AC: 834 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	18
Dann	Benign	0.97

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4795937; hg19: chr17-32907862; COSMIC: COSV58698265; COSMIC: COSV58698265;