rs6116651

Variant names:

• chr20-5106293-A-T
• rs6116651
• NM_001009925.2:c.117T>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001009925.2(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 NM_001009925.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.668
• Publications: 18 publications found

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: AD, SD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM230	NM_001009925.2	MANE Select	c.117T>A	p.Pro39Pro	synonymous	Exon 3 of 4	NP_001009925.1	Q96A57-1
	TMEM230	NM_001330987.2		c.117T>A	p.Pro39Pro	synonymous	Exon 3 of 4	NP_001317916.1	A0A087WTT2
	TMEM230	NM_001009924.2		c.117T>A	p.Pro39Pro	synonymous	Exon 4 of 5	NP_001009924.1	Q96A57-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM230	ENST00000202834.12	TSL:1 MANE Select	c.117T>A	p.Pro39Pro	synonymous	Exon 3 of 4	ENSP00000202834.7	Q96A57-1
	TMEM230	ENST00000612323.4	TSL:1	c.117T>A	p.Pro39Pro	synonymous	Exon 3 of 4	ENSP00000478641.1	A0A087WTT2
	TMEM230	ENST00000379299.6	TSL:1	c.117T>A	p.Pro39Pro	synonymous	Exon 3 of 4	ENSP00000368601.2	Q96A57-1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23120 AN: 152060 Hom.: 2441 Cov.: 32

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

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.: 33 AF XY: 0.105 AC XY: 76158 AN XY: 723318

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: 5 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

GnomAD4 genome AF: 0.152 AC: 23150 AN: 152178 Hom.: 2445 Cov.: 32 AF XY: 0.149 AC XY: 11062 AN XY: 74410

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: 4 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: 40 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7352 AN: 68000

Other (OTH) AF: 0.149 AC: 314 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.0
DANN	Benign	0.73
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6116651; hg19: chr20-5086939; COSMIC: COSV52533513;