20-5106074-GACAA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000342308.10(TMEM230):c.411+110_411+113del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,166,158 control chromosomes in the GnomAD database, including 2,654 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (119 hom., cov: 0)
  • Exomes 𝑓: 0.034 (2535 hom.)
• Consequence: TMEM230 ENST00000342308.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.263

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 -10 ACMG points.

• BP6: Variant 20-5106074-GACAA-G is Benign according to our data. Variant chr20-5106074-GACAA-G is described in ClinVar as [Benign]. Clinvar id is 1291916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM230	NM_001009923.2	c.411+110_411+113del		intron_variant		ENST00000342308.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM230	ENST00000342308.10	c.411+110_411+113del		intron_variant		2	NM_001009923.2

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 4966 AN: 126424 Hom.: 119 Cov.: 0

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0538

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0451

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0414

GnomAD4 exome AF: 0.0343 AC: 35705 AN: 1039638 Hom.: 2535 AF XY: 0.0346 AC XY: 17815 AN XY: 515222

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.0509

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.0428

Gnomad4 FIN exome AF: 0.0201

Gnomad4 NFE exome AF: 0.0347

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0393 AC: 4976 AN: 126520 Hom.: 119 Cov.: 0 AF XY: 0.0400 AC XY: 2428 AN XY: 60760

Gnomad4 AFR AF: 0.0526

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0538

Gnomad4 EAS AF: 0.0234

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.0409

Alfa AF: 0.0355 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs531414363; hg19: chr20-5086720;