Variant 15-72406686-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001080462.3(TMEM202):c.422T>A(p.Ile141Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,614,058 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

TMEM202
NM_001080462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.587

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:

TMEM202 (HGNC:):

TMEM202 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016244113).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM202	NM_001080462.3 linkuse as main transcript	c.422T>A	p.Ile141Asn	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 linkuse as main transcript	c.422T>A	p.Ile141Asn	missense_variant	3/5	5	NM_001080462.3	ENSP00000340212.3	A6NGA9
TMEM202	ENST00000649825.1 linkuse as main transcript	c.89T>A	p.Ile30Asn	missense_variant	3/5			ENSP00000497819.1	A0A3B3ITB0
TMEM202	ENST00000567679.1 linkuse as main transcript	c.166T>A	p.Ser56Thr	missense_variant	2/3	2		ENSP00000456083.1	H3BUG9
TMEM202	ENST00000568167.5 linkuse as main transcript	n.166T>A		non_coding_transcript_exon_variant	2/4	2		ENSP00000457632.1	H3BUG9

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000326

AC:

AN:

251400

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000266

AC:

389

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

180

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000506

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000236

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000533

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

Sep 27, 2021

The c.422T>A (p.I141N) alteration is located in exon 3 (coding exon 3) of the TMEM202 gene. This alteration results from a T to A substitution at nucleotide position 422, causing the isoleucine (I) at amino acid position 141 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.043

Sift

Uncertain

0.024

D;.

Sift4G

Uncertain

0.017

D;.

Polyphen

0.017

B;.

Vest4

0.55

MVP

0.16

MPC

0.19

ClinPred

0.017

GERP RS

1.8

Varity_R

0.061

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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