17-34626213-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304438.2(TMEM132E):c.154A>G(p.Thr52Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000631 in 1,426,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: TMEM132E NM_001304438.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09140748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E	NM_001304438.2	c.154A>G	p.Thr52Ala	missense_variant	2/9	ENST00000631683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E	ENST00000631683.2	c.154A>G	p.Thr52Ala	missense_variant	2/9	5	NM_001304438.2	P1
TMEM132E	ENST00000321639.7	c.154A>G	p.Thr52Ala	missense_variant	2/10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000631 AC: 9 AN: 1426554 Hom.: 0 Cov.: 32 AF XY: 0.00000708 AC XY: 5 AN XY: 706270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000822

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.154A>G (p.T52A) alteration is located in exon 2 (coding exon 2) of the TMEM132E gene. This alteration results from a A to G substitution at nucleotide position 154, causing the threonine (T) at amino acid position 52 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	19
Dann	Benign	0.86
DEOGEN2	Benign	0.0014	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.90	N;.
MutationTaster	Benign	0.69	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.63	N;.
REVEL	Benign	0.12
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.071	B;.
Vest4		0.28
MutPred		0.17		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.23
MPC		0.50
ClinPred		0.53	D
GERP RS		5.1
Varity_R		0.19
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-32953232;