Variant 7-138802927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001085429.2(TMEM213):c.182G>A(p.Arg61Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,595,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TMEM213
NM_001085429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.643

Variant links:

Genes affected

TMEM213 (HGNC:27220): (transmembrane protein 213) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM213 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028876185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM213	NM_001085429.2 linkuse as main transcript	c.182G>A	p.Arg61Gln	missense_variant	3/3	ENST00000442682.7	NP_001078898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM213	ENST00000442682.7 linkuse as main transcript	c.182G>A	p.Arg61Gln	missense_variant	3/3	1	NM_001085429.2	ENSP00000390407	P4	A2RRL7-1
TMEM213	ENST00000397602.7 linkuse as main transcript	c.179G>A	p.Arg60Gln	missense_variant	3/3	1		ENSP00000380727	A2	A2RRL7-3
TMEM213	ENST00000458494.1 linkuse as main transcript	c.110G>A	p.Arg37Gln	missense_variant	2/2	4		ENSP00000393891		A2RRL7-2
TMEM213	ENST00000413208.1 linkuse as main transcript	c.154+1529G>A		intron_variant		3		ENSP00000401570		A2RRL7-4

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152218

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:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000196

AC:

AN:

230108

Hom.:

AF XY:

0.000160

AC XY:

AN XY:

125106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000355

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000210

AC:

303

AN:

1443536

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

152

AN XY:

717220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000726

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000144

Gnomad4 FIN exome

AF:

0.000778

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.000318

GnomAD4 genome

AF:

0.000203

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74492

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:

0.000376

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000382

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000165

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

Jun 10, 2022

The c.182G>A (p.R61Q) alteration is located in exon 3 (coding exon 3) of the TMEM213 gene. This alteration results from a G to A substitution at nucleotide position 182, causing the arginine (R) at amino acid position 61 to be replaced by a glutamine (Q). 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

0.067

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0069

.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.15

.;N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.29

N;N;N

REVEL

Benign

0.010

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.059

MVP

0.014

MPC

0.58

ClinPred

0.041

GERP RS

-1.5

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