rs193920937

Positions:

• chr20-5106258-A-G

Variant summary

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

The ENST00000342308.10(TMEM230):​c.341T>C​(p.Val114Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM230 ENST00000342308.10 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.51

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM230	NM_001330987.2	c.152T>C	p.Val51Ala	missense_variant	3/4		NP_001317916.1
TMEM230	NM_001009924.2	c.152T>C	p.Val51Ala	missense_variant	4/5		NP_001009924.1
TMEM230	NM_001009925.2	c.152T>C	p.Val51Ala	missense_variant	3/4		NP_001009925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM230	ENST00000342308.10	c.341T>C	p.Val114Ala	missense_variant	4/5	2	NM_001009923.2	ENSP00000341364.6
TMEM230	ENST00000202834.11	c.152T>C	p.Val51Ala	missense_variant	3/4	1		ENSP00000202834.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461844 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.54
DEOGEN2	Benign	0.027	T;T;T;T;T;T;T;.;T;T
Eigen	Benign	-0.035
Eigen_PC	Benign	0.089
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	.;D;.;.;.;.;.;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;.;L;L;L;L;L;.;L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.2	.;.;N;N;N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.37	.;.;T;T;T;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0010, 0.045, 1.0	.;.;B;B;B;B;B;B;B;D
Vest4		0.59
MutPred		0.71		Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);.;Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);
MVP		0.27
MPC		1.2
ClinPred		0.86	D
GERP RS		5.2
Varity_R		0.10
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs193920937; hg19: chr20-5086904; COSMIC: COSV52533484;