20-5106293-A-G

Variant names:

• chr20-5106293-A-G
• NM_001009925.2:c.117T>C
• TMEM230 p.Pro39Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001009925.2(TMEM230):​c.117T>C​(p.Pro39Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P39P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM230 NM_001009925.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 0 publications found

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]

TMEM230 Gene-Disease associations (from GenCC):

• Parkinson disease

  Inheritance: SD, AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.668 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM230	NM_001009925.2	MANE Select	c.117T>C	p.Pro39Pro	synonymous	Exon 3 of 4	NP_001009925.1	Q96A57-1
	TMEM230	NM_001330987.2		c.117T>C	p.Pro39Pro	synonymous	Exon 3 of 4	NP_001317916.1	A0A087WTT2
	TMEM230	NM_001009924.2		c.117T>C	p.Pro39Pro	synonymous	Exon 4 of 5	NP_001009924.1	Q96A57-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM230	ENST00000202834.12	TSL:1 MANE Select	c.117T>C	p.Pro39Pro	synonymous	Exon 3 of 4	ENSP00000202834.7	Q96A57-1
	TMEM230	ENST00000612323.4	TSL:1	c.117T>C	p.Pro39Pro	synonymous	Exon 3 of 4	ENSP00000478641.1	A0A087WTT2
	TMEM230	ENST00000379299.6	TSL:1	c.117T>C	p.Pro39Pro	synonymous	Exon 3 of 4	ENSP00000368601.2	Q96A57-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		-0.67

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-5086939;