20-5100928-C-G

Position:

• chr20-5100928-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000342308.10(TMEM230):​c.415G>C​(p.Ala139Pro) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM230 ENST00000342308.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14592296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM230	NM_001009924.2	c.226G>C	p.Ala76Pro	missense_variant	5/5		NP_001009924.1
TMEM230	NM_001009925.2	c.226G>C	p.Ala76Pro	missense_variant	4/4		NP_001009925.1
TMEM230	NM_001330984.2	c.226G>C	p.Ala76Pro	missense_variant	5/5		NP_001317913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM230	ENST00000342308.10	c.415G>C	p.Ala139Pro	missense_variant	5/5	2	NM_001009923.2	ENSP00000341364.6
TMEM230	ENST00000202834.11	c.226G>C	p.Ala76Pro	missense_variant	4/4	1		ENSP00000202834.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 08, 2024

The c.415G>C (p.A139P) alteration is located in exon 5 (coding exon 5) of the TMEM230 gene. This alteration results from a G to C substitution at nucleotide position 415, causing the alanine (A) at amino acid position 139 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T;T;T;T;T;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.77	.;.;.;.;.;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;N;N;N;N;.;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.30	T;T;T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T;T;T
Polyphen		0.0010	B;B;B;B;B;B;B
Vest4		0.36
MutPred		0.44		Loss of catalytic residue at A76 (P = 0.0125);Loss of catalytic residue at A76 (P = 0.0125);Loss of catalytic residue at A76 (P = 0.0125);Loss of catalytic residue at A76 (P = 0.0125);Loss of catalytic residue at A76 (P = 0.0125);.;Loss of catalytic residue at A76 (P = 0.0125);
MVP		0.24
MPC		1.0
ClinPred		0.82	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-5081574;