9-137205411-G-C

Variant names:

• chr9-137205411-G-C
• NM_053045.2:c.4C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_053045.2(TMEM203):​c.4C>G​(p.Leu2Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM203 NM_053045.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

Genes affected

TMEM203 (HGNC:28217): (transmembrane protein 203) Involved in cellular calcium ion homeostasis. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28942698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM203	NM_053045.2	c.4C>G	p.Leu2Val	missense_variant	Exon 1 of 1	ENST00000343666.6	NP_444273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM203	ENST00000343666.6	c.4C>G	p.Leu2Val	missense_variant	Exon 1 of 1	6	NM_053045.2	ENSP00000375053.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	0.0088	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.068
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.071
Sift	Uncertain	0.029	D
Sift4G	Benign	0.074	T
Polyphen		0.77	P
Vest4		0.59
MutPred		0.27		Loss of helix (P = 0.1299);
MVP		0.043
MPC		2.0
ClinPred		0.80	D
GERP RS		1.1
Varity_R		0.082
gMVP		0.74

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: chr9-140099863;