20-5106078-A-AACAC

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+110insGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 544,376 control chromosomes in the GnomAD database, including 255 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (191 hom., cov: 0)
  • Exomes 𝑓: 0.039 (64 hom.)
• 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-AACAC is Benign according to our data. Variant chr20-5106078-A-AACAC is described in ClinVar as [Benign]. Clinvar id is 1265588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 6284 AN: 77802 Hom.: 192 Cov.: 0

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0468

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0768

GnomAD4 exome AF: 0.0389 AC: 18158 AN: 466548 Hom.: 64 AF XY: 0.0393 AC XY: 8983 AN XY: 228520

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.0471

Gnomad4 ASJ exome AF: 0.0240

Gnomad4 EAS exome AF: 0.0668

Gnomad4 SAS exome AF: 0.0209

Gnomad4 FIN exome AF: 0.0617

Gnomad4 NFE exome AF: 0.0378

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0807 AC: 6284 AN: 77828 Hom.: 191 Cov.: 0 AF XY: 0.0813 AC XY: 3062 AN XY: 37674

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.0845

Gnomad4 ASJ AF: 0.0468

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0771

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 23, 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;