Variant 7-98851547-C-T 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_152913.3(TMEM130):c.880G>A(p.Val294Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,614,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

TMEM130
NM_152913.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.497

Variant links:

Genes affected

TMEM130 (HGNC:25429): (transmembrane protein 130) Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM130 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=0.013188064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM130	NM_152913.3 linkuse as main transcript	c.880G>A	p.Val294Met	missense_variant	6/8	ENST00000339375.9	NP_690877.1
TMEM130	NM_001134450.2 linkuse as main transcript	c.880G>A	p.Val294Met	missense_variant	6/8		NP_001127922.1
TMEM130	NM_001134451.2 linkuse as main transcript	c.574G>A	p.Val192Met	missense_variant	5/7		NP_001127923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM130	ENST00000339375.9 linkuse as main transcript	c.880G>A	p.Val294Met	missense_variant	6/8	1	NM_152913.3	ENSP00000341256	P4	Q8N3G9-2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251098

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000265

AC:

388

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

222

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000309

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000359

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

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 30, 2022

The c.880G>A (p.V294M) alteration is located in exon 6 (coding exon 6) of the TMEM130 gene. This alteration results from a G to A substitution at nucleotide position 880, causing the valine (V) at amino acid position 294 to be replaced by a methionine (M). 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

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;.;T;.

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.095

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.44

MVP

0.19

MPC

0.69

ClinPred

0.066

GERP RS

2.3

Varity_R

0.030

gMVP

0.23

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