Variant 2-27034204-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017727.5(TMEM214):c.289A>G(p.Thr97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

TMEM214
NM_017727.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.555

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:

TMEM214 (HGNC:):

TMEM214 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0345622).

BP6

Variant 2-27034204-A-G is Benign according to our data. Variant chr2-27034204-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2471112.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM214	NM_017727.5 linkuse as main transcript	c.289A>G	p.Thr97Ala	missense_variant	2/17	ENST00000238788.14	NP_060197.4	Q6NUQ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM214	ENST00000238788.14 linkuse as main transcript	c.289A>G	p.Thr97Ala	missense_variant	2/17	1	NM_017727.5	ENSP00000238788.9		Q6NUQ4-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152052

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249556

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74298

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:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.035

DANN

Benign

0.54

DEOGEN2

Benign

0.0061

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.19

Sift

Benign

0.51

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0

B;B

Vest4

0.067

MutPred

0.14

Loss of phosphorylation at T97 (P = 0.0053);Loss of phosphorylation at T97 (P = 0.0053);

MVP

0.16

MPC

0.13

ClinPred

0.020

GERP RS

-5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.12

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