Variant 7-98860267-T-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 ENST00000339375.9(TMEM130):c.463A>T(p.Thr155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TMEM130
ENST00000339375.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

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

TMEM130 links:

TMEM130 (HGNC:):

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=0.08611059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM130	NM_152913.3 linkuse as main transcript	c.463A>T	p.Thr155Ser	missense_variant	3/8	ENST00000339375.9	NP_690877.1	Q8N3G9-2
TMEM130	NM_001134450.2 linkuse as main transcript	c.463A>T	p.Thr155Ser	missense_variant	3/8		NP_001127922.1	Q8N3G9-1
TMEM130	NM_001134451.2 linkuse as main transcript	c.157A>T	p.Thr53Ser	missense_variant	2/7		NP_001127923.1	Q8N3G9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM130	ENST00000339375.9 linkuse as main transcript	c.463A>T	p.Thr155Ser	missense_variant	3/8	1	NM_152913.3	ENSP00000341256.4		Q8N3G9-2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151800

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251004

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135664

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726974

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:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74102

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

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

Mar 22, 2022

The c.463A>T (p.T155S) alteration is located in exon 3 (coding exon 3) of the TMEM130 gene. This alteration results from a A to T substitution at nucleotide position 463, causing the threonine (T) at amino acid position 155 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.034

T;.;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.086

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.15

T;T;T;D

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.065

B;P;.;B

Vest4

0.19

MutPred

0.33

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;.;

MVP

0.14

MPC

0.20

ClinPred

0.22

GERP RS

4.3

Varity_R

0.049

gMVP

0.29

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