Genetic Variant TMEM214:p.Val351Met (chr2-27037601-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

41 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM214	NM_017727.5 link	c.1051G>A	p.Val351Met	missense_variant	Exon 9 of 17	ENST00000238788.14	NP_060197.4	Q6NUQ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM214	ENST00000238788.14 link	c.1051G>A	p.Val351Met	missense_variant	Exon 9 of 17	1	NM_017727.5	ENSP00000238788.9		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

GnomAD2 exomes

AF:

0.317

AC:

79143

AN:

249570

AF XY:

0.311

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 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

African (AFR)

AF:

0.439

AC:

14710

AN:

33480

American (AMR)

AF:

0.456

AC:

20380

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

8094

AN:

26136

East Asian (EAS)

AF:

0.0569

AC:

2260

AN:

39700

South Asian (SAS)

AF:

0.292

AC:

25216

AN:

86258

European-Finnish (FIN)

AF:

0.274

AC:

14661

AN:

53420

Middle Eastern (MID)

AF:

0.324

AC:

1867

AN:

5768

European-Non Finnish (NFE)

AF:

0.303

AC:

337331

AN:

1111970

Other (OTH)

AF:

0.301

AC:

18159

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19414

38828

58241

77655

97069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10964

21928

32892

43856

54820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.341

AC:

51765

AN:

151906

Hom.:

9342

Cov.:

AF XY:

0.338

AC XY:

25099

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.432

AC:

17894

AN:

41374

American (AMR)

AF:

0.394

AC:

6009

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1077

AN:

3470

East Asian (EAS)

AF:

0.0715

AC:

370

AN:

5174

South Asian (SAS)

AF:

0.280

AC:

1349

AN:

4824

European-Finnish (FIN)

AF:

0.270

AC:

2854

AN:

10566

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.310

AC:

21025

AN:

67926

Other (OTH)

AF:

0.328

AC:

691

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1678

3356

5035

6713

8391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.322

Hom.:

36446

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

(source)

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;.

PhyloP100

9.3

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

PromoterAI

-0.022

Neutral

(source)

Varity_R

0.20

gMVP

0.43

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over