rs6116651

Positions:

• chr20-5106293-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001009923.2(TMEM230):​c.306T>A​(p.Pro102=) 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_001009923.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.668

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
TMEM230	NM_001009923.2	c.306T>A	p.Pro102=	synonymous_variant	4/5	ENST00000342308.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM230	ENST00000342308.10	c.306T>A	p.Pro102=	synonymous_variant	4/5	2	NM_001009923.2

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

GnomAD3 exomes AF: 0.0997 AC: 24264 AN: 243446 Hom.: 1717 AF XY: 0.0964 AC XY: 12697 AN XY: 131664

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 SAS exome AF: 0.0581

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

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.0717

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0621

Gnomad4 FIN exome AF: 0.0685

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.115

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0558

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.149

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.0
DANN	Benign	0.73

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

Other links and lift over

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