Variant 12-125326673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052907.3(TMEM132B):c.50G>A(p.Gly17Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,606,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TMEM132B
NM_052907.3 missense, splice_region

Scores

Splicing: ADA: 0.0002300

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.447

Variant links:

Genes affected

TMEM132B (HGNC:29397): (transmembrane protein 132B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM132B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24015206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132B	NM_001366854.1 link	c.68-22779G>A		intron_variant		ENST00000682704.1	NP_001353783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM132B	ENST00000682704.1 link	c.68-22779G>A		intron_variant			NM_001366854.1	ENSP00000507790.1	A0A804HK64
TMEM132B	ENST00000299308.7 link	c.50G>A	p.Gly17Glu	missense_variant, splice_region_variant	1/9	5		ENSP00000299308.3	Q14DG7-1
TMEM132B	ENST00000535330.1 link	n.123G>A		splice_region_variant, non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000940

AC:

AN:

234070

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

126104

show subpopulations

Gnomad AFR exome

AF:

0.0000703

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

221

AN:

1454184

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

722224

show subpopulations

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:

0.000195

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.000105

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000362

AC:

ExAC

AF:

0.0000745

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.50G>A (p.G17E) alteration is located in exon 1 (coding exon 1) of the TMEM132B gene. This alteration results from a G to A substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 to be replaced by a glutamic acid (E). 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

0.088

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.5

DANN

Benign

0.72

DEOGEN2

Benign

0.011

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.37

M_CAP

Benign

0.0037

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.30

PROVEAN

Benign

0.69

REVEL

Benign

0.15

Sift

Benign

0.94

Sift4G

Benign

0.99

Polyphen

0.99

Vest4

0.45

MVP

0.18

MPC

0.33

ClinPred

0.032

GERP RS

2.1

Varity_R

0.055

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.062

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over