Variant 7-138802956-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001085429.2(TMEM213):c.211G>A(p.Gly71Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000223 in 1,612,248 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

TMEM213
NM_001085429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.45

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM213	NM_001085429.2 linkuse as main transcript	c.211G>A	p.Gly71Ser	missense_variant	3/3	ENST00000442682.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM213	ENST00000442682.7 linkuse as main transcript	c.211G>A	p.Gly71Ser	missense_variant	3/3	1	NM_001085429.2	P4	A2RRL7-1
TMEM213	ENST00000397602.7 linkuse as main transcript	c.208G>A	p.Gly70Ser	missense_variant	3/3	1		A2	A2RRL7-3
TMEM213	ENST00000458494.1 linkuse as main transcript	c.139G>A	p.Gly47Ser	missense_variant	2/2	4			A2RRL7-2
TMEM213	ENST00000413208.1 linkuse as main transcript	c.154+1558G>A		intron_variant		3			A2RRL7-4

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000245

AC:

AN:

245144

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

133260

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.0000950

Gnomad NFE exome

AF:

0.000354

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.000227

AC:

331

AN:

1460020

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

167

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.0000758

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000191

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000215

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000653

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

Oct 04, 2022

The c.211G>A (p.G71S) 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 211, causing the glycine (G) at amino acid position 71 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

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.36

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-0.48

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.91

MVP

0.11

MPC

0.92

ClinPred

0.81

GERP RS

5.8

Varity_R

0.71

gMVP

0.57

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