Variant 20-5100832-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001009923.2(TMEM230):c.511C>T(p.Arg171Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,614,082 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 3 hom. )

Consequence

TMEM230
NM_001009923.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

TMEM230 (HGNC:15876): (transmembrane protein 230) This gene encodes a multi-pass transmembrane protein that belongs to the TMEM134/TMEM230 protein family. The encoded protein localizes to secretory and recycling vesicle in the neuron and may be involved in synaptic vesicles trafficking and recycling. Mutations in this gene may be linked to familial Parkinson's disease. [provided by RefSeq, Mar 2017]

TMEM230 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011056185).

BP6

Variant 20-5100832-G-A is Benign according to our data. Variant chr20-5100832-G-A is described in ClinVar as [Benign]. Clinvar id is 2046219.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM230	NM_001009923.2 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/5	ENST00000342308.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM230	ENST00000342308.10 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/5	2	NM_001009923.2		Q96A57-2

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

283

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00245

AC:

616

AN:

251486

Hom.:

AF XY:

0.00264

AC XY:

359

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00218

AC:

3193

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

1637

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.00951

Gnomad4 NFE exome

AF:

0.00217

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00186

AC:

283

AN:

152280

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00848

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00298

AC:

362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.10

T;T;T;T;T;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.74

M_CAP

Benign

0.034

MetaRNN

Benign

0.011

T;T;T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.6

M;M;M;M;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.7

D;D;D;D;D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.017

D;D;D;D;D;T;D

Sift4G

Uncertain

0.036

D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D

Vest4

0.46

MVP

0.57

MPC

1.2

ClinPred

0.035

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.92

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