Variant rs1124649 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017727.5(TMEM214):c.1051G>A(p.Val351Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,613,758 control chromosomes in the GnomAD database, including 79,197 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9342 hom., cov: 31)

Exomes 𝑓: 0.30 ( 69855 hom. )

Consequence

TMEM214
NM_017727.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.35

Variant links:

Genes affected

TMEM214 (HGNC:25983): (transmembrane protein 214) Predicted to be involved in apoptotic process. Located in several cellular components, including Golgi apparatus; cytoplasmic microtubule; and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMEM214 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00463894).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM214	NM_017727.5 linkuse as main transcript	c.1051G>A	p.Val351Met	missense_variant	9/17	ENST00000238788.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM214	ENST00000238788.14 linkuse as main transcript	c.1051G>A	p.Val351Met	missense_variant	9/17	1	NM_017727.5	P1	Q6NUQ4-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51698

AN:

151788

Hom.:

9320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.324

GnomAD3 exomes

AF:

0.317

AC:

79143

AN:

249570

Hom.:

13883

AF XY:

0.311

AC XY:

42129

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.0684

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.303

AC:

442678

AN:

1461852

Hom.:

69855

Cov.:

AF XY:

0.302

AC XY:

219598

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.310

Gnomad4 EAS exome

AF:

0.0569

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.341

AC:

51765

AN:

151906

Hom.:

9342

Cov.:

AF XY:

0.338

AC XY:

25099

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.432

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.0715

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.319

Hom.:

19161

Bravo

AF:

0.357

TwinsUK

AF:

0.291

AC:

1079

ALSPAC

AF:

0.303

AC:

1169

ESP6500AA

AF:

0.415

AC:

1640

ESP6500EA

AF:

0.306

AC:

2550

ExAC

AF:

0.316

AC:

38192

Asia WGS

AF:

0.218

AC:

756

AN:

3478

EpiCase

AF:

0.324

EpiControl

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

2.5e-7

P;P

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.021

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.25

MPC

0.59

ClinPred

0.027

GERP RS

5.7

Varity_R

0.20

gMVP

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over