17-34626238-A-T

Variant summary

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

The NM_001304438.2(TMEM132E):c.179A>T(p.Glu60Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E60E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM132E NM_001304438.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E	NM_001304438.2	c.179A>T	p.Glu60Val	missense_variant	2/9	ENST00000631683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E	ENST00000631683.2	c.179A>T	p.Glu60Val	missense_variant	2/9	5	NM_001304438.2	P1
TMEM132E	ENST00000321639.7	c.179A>T	p.Glu60Val	missense_variant	2/10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Feb 06, 2023

The c.179A>T (p.E60V) alteration is located in exon 2 (coding exon 2) of the TMEM132E gene. This alteration results from a A to T substitution at nucleotide position 179, causing the glutamic acid (E) at amino acid position 60 to be replaced by a valine (V). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	0.80	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.7	D;.
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.53	P;.
Vest4		0.52
MutPred		0.36		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.17
MPC		1.2
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.67
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-32953257;