Variant 7-98848181-A-T 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_152913.3(TMEM130):c.1147T>A(p.Cys383Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TMEM130
NM_152913.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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 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=0.16930032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM130	NM_152913.3 linkuse as main transcript	c.1147T>A	p.Cys383Ser	missense_variant	8/8	ENST00000339375.9	NP_690877.1
TMEM130	NM_001134450.2 linkuse as main transcript	c.1183T>A	p.Cys395Ser	missense_variant	8/8		NP_001127922.1
TMEM130	NM_001134451.2 linkuse as main transcript	c.841T>A	p.Cys281Ser	missense_variant	7/7		NP_001127923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM130	ENST00000339375.9 linkuse as main transcript	c.1147T>A	p.Cys383Ser	missense_variant	8/8	1	NM_152913.3	ENSP00000341256	P4	Q8N3G9-2
TMEM130	ENST00000416379.6 linkuse as main transcript	c.1183T>A	p.Cys395Ser	missense_variant	8/8	1		ENSP00000413163	A1	Q8N3G9-1
TMEM130	ENST00000345589.4 linkuse as main transcript	c.841T>A	p.Cys281Ser	missense_variant	7/7	1		ENSP00000330262		Q8N3G9-3
TMEM130	ENST00000450876.5 linkuse as main transcript	c.895T>A	p.Cys299Ser	missense_variant	8/8	2		ENSP00000390200

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152148

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251236

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135826

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727230

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000151

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 30, 2022

The c.1183T>A (p.C395S) alteration is located in exon 8 (coding exon 8) of the TMEM130 gene. This alteration results from a T to A substitution at nucleotide position 1183, causing the cysteine (C) at amino acid position 395 to be replaced by a serine (S). 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

0.29

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;.;T;.

Eigen

Benign

0.089

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.;.;.

MutationTaster

Benign

0.77

N;N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.30

N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.060

T;T;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.94

P;P;.;P

Vest4

0.44

MutPred

0.62

Gain of disorder (P = 0.0258);.;.;.;

MVP

0.27

MPC

0.46

ClinPred

0.37

GERP RS

3.1

Varity_R

0.21

gMVP

0.52

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