Genetic Variant NM_053045.2:c.4C>T (chr9-137205411-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053045.2(TMEM203):c.4C>T(p.Leu2Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,565,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TMEM203
NM_053045.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Publications

1 publications found

Variant links:

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]

TMEM203 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034570575).

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>T	p.Leu2Phe	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>T	p.Leu2Phe	missense	Exon 1 of 1	ENSP00000375053.4	Q969S6

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000228

AC:

AN:

188184

AF XY:

0.000234

show subpopulations

Gnomad AFR exome

AF:

0.0000888

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000212

Gnomad FIN exome

AF:

0.000762

Gnomad NFE exome

AF:

0.000201

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.000211

AC:

298

AN:

1412816

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

149

AN XY:

697182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32304

American (AMR)

AF:

0.0000259

AC:

AN:

38650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.0000530

AC:

AN:

37714

South Asian (SAS)

AF:

0.00

AC:

AN:

82114

European-Finnish (FIN)

AF:

0.00117

AC:

AN:

49638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4516

European-Non Finnish (NFE)

AF:

0.000188

AC:

204

AN:

1084604

Other (OTH)

AF:

0.000568

AC:

AN:

58130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41596

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000199

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000345

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Benign

0.13

Eigen_PC

Benign

0.074

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.076

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

PhyloP100

2.4

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.84

REVEL

Benign

0.17

Sift

Benign

0.35

Sift4G

Benign

0.30

Polyphen

0.99

Vest4

0.61

MVP

0.043

MPC

1.6

ClinPred

0.045

GERP RS

1.1

PromoterAI

0.087

Neutral

(source)

Varity_R

0.049

gMVP

0.75

Mutation Taster

=59/41

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over