chr20-5101102-C-G

Position:

• chr20-5101102-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000342308.10(TMEM230):​c.412-171G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 151,964 control chromosomes in the GnomAD database, including 466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.066 (466 hom., cov: 32)
• Consequence: TMEM230 ENST00000342308.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.348

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 20-5101102-C-G is Benign according to our data. Variant chr20-5101102-C-G is described in ClinVar as [Benign]. Clinvar id is 1247220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM230	NM_001009923.2	c.412-171G>C		intron_variant		ENST00000342308.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM230	ENST00000342308.10	c.412-171G>C		intron_variant		2	NM_001009923.2

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10106 AN: 151850 Hom.: 467 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0846

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0665 AC: 10101 AN: 151964 Hom.: 466 Cov.: 32 AF XY: 0.0644 AC XY: 4787 AN XY: 74318

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0637

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0488

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0837

Alfa AF: 0.0800 Hom.: 73

Bravo AF: 0.0647

Asia WGS AF: 0.0210 AC: 76 AN: 3476

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	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs41282108; hg19: chr20-5081748;