Variant 12-129074630-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133448.3(TMEM132D):c.2545C>T(p.Leu849Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,068 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

TMEM132D
NM_133448.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

TMEM132D (HGNC:29411): (transmembrane protein 132D)

TMEM132D links:

LOC124903086 (HGNC:):

LOC124903086 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0075220764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3 linkuse as main transcript	c.2545C>T	p.Leu849Phe	missense_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1 linkuse as main transcript	n.87-276G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7 linkuse as main transcript	c.2545C>T	p.Leu849Phe	missense_variant	9/9	1	NM_133448.3	P1	Q14C87-1
TMEM132D	ENST00000389441.8 linkuse as main transcript	c.1159C>T	p.Leu387Phe	missense_variant	4/4	1			Q14C87-2

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

111

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000644

AC:

162

AN:

251488

Hom.:

AF XY:

0.000662

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.00104

AC:

1517

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

734

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152174

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000968

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.000675

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00172

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

Aug 02, 2022

The c.2545C>T (p.L849F) alteration is located in exon 9 (coding exon 9) of the TMEM132D gene. This alteration results from a C to T substitution at nucleotide position 2545, causing the leucine (L) at amino acid position 849 to be replaced by a phenylalanine (F). 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

0.068

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.41

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.035

Sift

Benign

0.72

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0090

B;P

Vest4

0.031

MVP

0.093

MPC

0.48

ClinPred

0.035

GERP RS

2.3

Varity_R

0.043

gMVP

0.21

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