Genetic Variant ENST00000612323.4:c.117T>A (chr20-5106293-A-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000612323.4(TMEM230):c.117T>A(p.Pro39Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,606,410 control chromosomes in the GnomAD database, including 12,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2445 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9585 hom. )

Consequence

TMEM230
ENST00000612323.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.668

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

Parkinson disease
Inheritance: SD, AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics

TMEM230 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 20-5106293-A-T is Benign according to our data. Variant chr20-5106293-A-T is described in ClinVar as Benign. ClinVar VariationId is 1265859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.668 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
TMEM230	NM_001330987.2 link	c.117T>A	p.Pro39Pro	synonymous_variant	Exon 3 of 4	NP_001317916.1	A0A087WTT2
TMEM230	NM_001009924.2 link	c.117T>A	p.Pro39Pro	synonymous_variant	Exon 4 of 5	NP_001009924.1	Q96A57-1
TMEM230	NM_001009925.2 link	c.117T>A	p.Pro39Pro	synonymous_variant	Exon 3 of 4	NP_001009925.1	Q96A57-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM230	ENST00000202834.12 link	c.117T>A	p.Pro39Pro	synonymous_variant	Exon 3 of 4	1		ENSP00000202834.7		Q96A57-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23120

AN:

152060

Hom.:

2441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0555

Gnomad FIN

AF:

0.0595

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.150

GnomAD2 exomes

AF:

0.0997

AC:

24264

AN:

243446

AF XY:

0.0964

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.0665

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.0655

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.107

AC:

155483

AN:

1454232

Hom.:

9585

Cov.:

AF XY:

0.105

AC XY:

76158

AN XY:

723318

show subpopulations

African (AFR)

AF:

0.308

AC:

10115

AN:

32884

American (AMR)

AF:

0.0717

AC:

3046

AN:

42464

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

3923

AN:

25766

East Asian (EAS)

AF:

0.000126

AC:

AN:

39600

South Asian (SAS)

AF:

0.0621

AC:

5249

AN:

84476

European-Finnish (FIN)

AF:

0.0685

AC:

3656

AN:

53358

Middle Eastern (MID)

AF:

0.156

AC:

895

AN:

5732

European-Non Finnish (NFE)

AF:

0.110

AC:

121664

AN:

1109896

Other (OTH)

AF:

0.115

AC:

6930

AN:

60056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

6793

13586

20380

27173

33966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4480

8960

13440

17920

22400

<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:

0.152

AC:

23150

AN:

152178

Hom.:

2445

Cov.:

AF XY:

0.149

AC XY:

11062

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.296

AC:

12262

AN:

41472

American (AMR)

AF:

0.108

AC:

1645

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

512

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0558

AC:

269

AN:

4822

European-Finnish (FIN)

AF:

0.0595

AC:

632

AN:

10620

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7352

AN:

68000

Other (OTH)

AF:

0.149

AC:

314

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

968

1936

2904

3872

4840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.124

Hom.:

477

Bravo

AF:

0.162

Asia WGS

AF:

0.0450

AC:

158

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.118

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.0

(source)

DANN

Benign

0.73

PhyloP100

-0.67

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over