20-5106078-A-AAC

Variant summary

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

The ENST00000342308.10(TMEM230):c.411+109_411+110insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 446,652 control chromosomes in the GnomAD database, including 475 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (5085 hom., cov: 0)
  • Exomes 𝑓: 0.26 (475 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM230 ENST00000342308.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.315

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 20-5106078-A-AAC is Benign according to our data. Variant chr20-5106078-A-AAC is described in ClinVar as [Benign]. Clinvar id is 1275019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM230	NM_001009923.2	c.411+109_411+110insGT		intron_variant		ENST00000342308.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM230	ENST00000342308.10	c.411+109_411+110insGT		intron_variant		2	NM_001009923.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 36395 AN: 77372 Hom.: 5085 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.259 AC: 115574 AN: 446652 Hom.: 475 AF XY: 0.262 AC XY: 57387 AN XY: 218632

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.470 AC: 36397 AN: 77400 Hom.: 5085 Cov.: 0 AF XY: 0.472 AC XY: 17689 AN XY: 37476

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.458

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61087830; hg19: chr20-5086724;