Variant chr11-60927846-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000453848.7(TMEM132A):c.521C>G(p.Ala174Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,609,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMEM132A
ENST00000453848.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

TMEM132A (HGNC:31092): (transmembrane protein 132A) This gene encodes a protein that is highly similar to the rat Grp78-binding protein (GBP). Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

TMEM132A links:

TMEM132A (HGNC:):

TMEM132A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36423346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132A	NM_178031.3 linkuse as main transcript	c.521C>G	p.Ala174Gly	missense_variant	3/11	ENST00000453848.7	NP_821174.1	Q24JP5-1
TMEM132A	NM_017870.4 linkuse as main transcript	c.521C>G	p.Ala174Gly	missense_variant	3/11		NP_060340.2	Q24JP5-2
TMEM132A	XM_017017951.3 linkuse as main transcript	c.560C>G	p.Ala187Gly	missense_variant	2/10		XP_016873440.1
TMEM132A	XM_017017952.3 linkuse as main transcript	c.560C>G	p.Ala187Gly	missense_variant	2/10		XP_016873441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132A	ENST00000453848.7 linkuse as main transcript	c.521C>G	p.Ala174Gly	missense_variant	3/11	1	NM_178031.3	ENSP00000405823.2		Q24JP5-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242662

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132558

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456958

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724804

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000945

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 15, 2023

The c.521C>G (p.A174G) alteration is located in exon 3 (coding exon 3) of the TMEM132A gene. This alteration results from a C to G substitution at nucleotide position 521, causing the alanine (A) at amino acid position 174 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0091

T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.069

Sift

Benign

0.077

T;T

Sift4G

Uncertain

0.022

D;D

Polyphen

0.97

D;D

Vest4

0.46

MutPred

0.23

Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);

MVP

0.47

MPC

0.91

ClinPred

0.48

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.066

gMVP

0.54

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

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