Variant chr15-72406649-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_001080462.3(TMEM202):c.385A>G(p.Ile129Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TMEM202
NM_001080462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.676

Variant links:

Genes affected

TMEM202 (HGNC:33733): (transmembrane protein 202) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM202 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=0.07160565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM202	NM_001080462.3 link	c.385A>G	p.Ile129Val	missense_variant	3/5	ENST00000341689.4	NP_001073931.1	A6NGA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM202	ENST00000341689.4 link	c.385A>G	p.Ile129Val	missense_variant	3/5	5	NM_001080462.3	ENSP00000340212.3	A6NGA9
TMEM202	ENST00000649825.1 link	c.52A>G	p.Ile18Val	missense_variant	3/5			ENSP00000497819.1	A0A3B3ITB0
TMEM202	ENST00000567679.1 link	c.129A>G	p.Pro43Pro	synonymous_variant	2/3	2		ENSP00000456083.1	H3BUG9
TMEM202	ENST00000568167.5 link	n.129A>G		non_coding_transcript_exon_variant	2/4	2		ENSP00000457632.1	H3BUG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251346

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000116

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 02, 2024

The c.385A>G (p.I129V) alteration is located in exon 3 (coding exon 3) of the TMEM202 gene. This alteration results from a A to G substitution at nucleotide position 385, causing the isoleucine (I) at amino acid position 129 to be replaced by a valine (V). 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

0.095

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.9

DANN

Benign

0.55

DEOGEN2

Benign

0.0059

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.19

N;.

REVEL

Benign

0.070

Sift

Benign

0.31

T;.

Sift4G

Benign

0.63

T;.

Polyphen

0.047

B;.

Vest4

0.17

MutPred

0.33

Loss of MoRF binding (P = 0.2851);.;

MVP

0.030

MPC

0.18

ClinPred

0.063

GERP RS

1.7

Varity_R

0.028

gMVP

0.17

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