Variant 2-219547947-A-G 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_001005209.3(TMEM198):c.608A>G(p.Glu203Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000195 in 1,592,482 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 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TMEM198
NM_001005209.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Variant links:

Genes affected

TMEM198 (HGNC:33704): (transmembrane protein 198) Involved in positive regulation of canonical Wnt signaling pathway. Located in cytoplasmic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM198 links:

OBSL1 (HGNC:):

OBSL1 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=0.118418485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM198	NM_001005209.3 linkuse as main transcript	c.608A>G	p.Glu203Gly	missense_variant	3/5	ENST00000373883.4	NP_001005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM198	ENST00000373883.4 linkuse as main transcript	c.608A>G	p.Glu203Gly	missense_variant	3/5	1	NM_001005209.3	ENSP00000362990	P1
TMEM198	ENST00000344458.6 linkuse as main transcript	c.608A>G	p.Glu203Gly	missense_variant	4/6	1		ENSP00000343507	P1
TMEM198	ENST00000421791.1 linkuse as main transcript	c.608A>G	p.Glu203Gly	missense_variant	3/3	2		ENSP00000388087

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

215556

Hom.:

AF XY:

0.0000252

AC XY:

AN XY:

118862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000928

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:

0.00

Gnomad OTH exome

AF:

0.000544

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1440244

Hom.:

Cov.:

AF XY:

0.00000838

AC XY:

AN XY:

716170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000208

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:

0.00

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000105

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

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:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000204

ExAC

AF:

0.00000829

AC:

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

Jul 17, 2023

The c.608A>G (p.E203G) alteration is located in exon 3 (coding exon 2) of the TMEM198 gene. This alteration results from a A to G substitution at nucleotide position 608, causing the glutamic acid (E) at amino acid position 203 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

0.13

BayesDel_addAF

Benign

-0.0086

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.0077

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

M;.;M

MutationTaster

Benign

0.97

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.069

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.014

B;.;B

Vest4

0.22

MVP

0.18

MPC

0.80

ClinPred

0.83

GERP RS

4.2

Varity_R

0.29

gMVP

0.79

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