Variant 2-219547934-C-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 NM_001005209.3(TMEM198):c.595C>A(p.Arg199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM198
NM_001005209.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.912

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:

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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=0.17150405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM198	NM_001005209.3 linkuse as main transcript	c.595C>A	p.Arg199Ser	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.595C>A	p.Arg199Ser	missense_variant	3/5	1	NM_001005209.3	ENSP00000362990	P1
TMEM198	ENST00000344458.6 linkuse as main transcript	c.595C>A	p.Arg199Ser	missense_variant	4/6	1		ENSP00000343507	P1
TMEM198	ENST00000421791.1 linkuse as main transcript	c.595C>A	p.Arg199Ser	missense_variant	3/3	2		ENSP00000388087

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717668

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 24, 2024

The c.595C>A (p.R199S) alteration is located in exon 3 (coding exon 2) of the TMEM198 gene. This alteration results from a C to A substitution at nucleotide position 595, causing the arginine (R) at amino acid position 199 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

0.16

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0043

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.67

.;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N

MutationTaster

Benign

0.93

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.12

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.88

T;T;T

Sift4G

Benign

0.75

T;T;T

Polyphen

0.27

B;.;B

Vest4

0.31

MutPred

0.45

Loss of methylation at R199 (P = 0.0312);Loss of methylation at R199 (P = 0.0312);Loss of methylation at R199 (P = 0.0312);

MVP

0.17

MPC

0.74

ClinPred

0.63

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over