chr9-137205411-G-C

Variant names:

• chr9-137205411-G-C
• rs373290215
• NM_053045.2:c.4C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM203 NM_053045.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053045.2. 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
	TMEM203	NM_053045.2	MANE Select	c.4C>G	p.Leu2Val	missense	Exon 1 of 1	NP_444273.1	Q969S6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM203	ENST00000343666.6	TSL:6 MANE Select	c.4C>G	p.Leu2Val	missense	Exon 1 of 1	ENSP00000375053.4	Q969S6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.4
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
PromoterAI		0.084	Neutral
Varity_R		0.082
gMVP		0.74
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs373290215; hg19: chr9-140099863;