dbSNP rs555049321: TMEM132E:p.Pro41Gln (chr17-34626181-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304438.2(TMEM132E):c.122C>A(p.Pro41Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P41L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TMEM132E
NM_001304438.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167

Publications

0 publications found

Variant links:

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]

TMEM132E Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 99
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

TMEM132E links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12160823).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304438.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132E	NM_001304438.2	MANE Select	c.122C>A	p.Pro41Gln	missense	Exon 2 of 9	NP_001291367.1	Q6IEE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132E	ENST00000631683.2	TSL:5 MANE Select	c.122C>A	p.Pro41Gln	missense	Exon 2 of 9	ENSP00000487800.2	Q6IEE7
	TMEM132E	ENST00000321639.7	TSL:5	c.122C>A	p.Pro41Gln	missense	Exon 2 of 10	ENSP00000316532.5	A0A494BWY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412074

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32434

American (AMR)

AF:

0.00

AC:

AN:

38218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25206

East Asian (EAS)

AF:

0.00

AC:

AN:

37088

South Asian (SAS)

AF:

0.00

AC:

AN:

80416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4378

European-Non Finnish (NFE)

AF:

9.20e-7

AC:

AN:

1087162

Other (OTH)

AF:

0.00

AC:

AN:

58376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.70

M_CAP

Benign

0.0060

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.17

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

REVEL

Benign

0.024

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.016

Polyphen

0.0020

Vest4

0.40

MutPred

0.20

Gain of sheet (P = 0.0101)

MVP

0.048

MPC

0.44

ClinPred

0.53

GERP RS

1.8

Varity_R

0.082

gMVP

0.29

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over