17-34581017-C-T

Position:

• chr17-34581017-C-T

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.-60C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,444,540 control chromosomes in the GnomAD database, including 18,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1663 hom., cov: 35)
  • Exomes 𝑓: 0.16 (17043 hom.)
• Consequence: TMEM132E NM_001304438.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0710

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=-0.19).
• BP6: Variant 17-34581017-C-T is Benign according to our data. Variant chr17-34581017-C-T is described in ClinVar as [Benign]. Clinvar id is 1264289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132E	NM_001304438.2	c.-60C>T		5_prime_UTR_premature_start_codon_gain_variant	1/9	ENST00000631683.2	NP_001291367.1
TMEM132E	NM_001304438.2	c.-60C>T		5_prime_UTR_variant	1/9	ENST00000631683.2	NP_001291367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132E	ENST00000631683.2	c.-60C>T		5_prime_UTR_premature_start_codon_gain_variant	1/9	5	NM_001304438.2	ENSP00000487800.2
TMEM132E	ENST00000631683.2	c.-60C>T		5_prime_UTR_variant	1/9	5	NM_001304438.2	ENSP00000487800.2
TMEM132E	ENST00000321639.7	c.-60C>T		5_prime_UTR_premature_start_codon_gain_variant	1/10	5		ENSP00000316532.5
TMEM132E	ENST00000321639.7	c.-60C>T		5_prime_UTR_variant	1/10	5		ENSP00000316532.5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21748 AN: 152164 Hom.: 1666 Cov.: 35

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.159 AC: 205099 AN: 1292258 Hom.: 17043 Cov.: 19 AF XY: 0.157 AC XY: 100386 AN XY: 639878

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0608

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0864

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.143 AC: 21746 AN: 152282 Hom.: 1663 Cov.: 35 AF XY: 0.142 AC XY: 10550 AN XY: 74454

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0902

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.121

Alfa AF: 0.109 Hom.: 171

Bravo AF: 0.132

Asia WGS AF: 0.0810 AC: 282 AN: 3474

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	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	14
DANN	Uncertain	0.97

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: rs79263247; hg19: chr17-32908036; COSMIC: COSV58694517; COSMIC: COSV58694517;