dbSNP rs543455233: TMEM200C:p.Ser400Gly (chr18-5890866-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395400.1(TMEM200C):c.1198A>G(p.Ser400Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 682,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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. S400I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

TMEM200C
NM_001395400.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

Variant links:

Genes affected

TMEM200C (HGNC:37208): (transmembrane protein 200C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM200C links:

ENSG00000264449 (HGNC:):

ENSG00000264449 links:

MIR3976HG (HGNC:51104): (MIR3976 host gene)

MIR3976HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059322864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200C	NM_001395400.1 link	c.1198A>G	p.Ser400Gly	missense_variant	Exon 2 of 2	ENST00000383490.3	NP_001382329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM200C	ENST00000383490.3 link	c.1198A>G	p.Ser400Gly	missense_variant	Exon 2 of 2	6	NM_001395400.1	ENSP00000372982.2	A6NKL6
TMEM200C	ENST00000581347.2 link	c.1198A>G	p.Ser400Gly	missense_variant	Exon 3 of 3	5		ENSP00000463375.1	A6NKL6
ENSG00000264449	ENST00000577694.1 link	n.199+1693T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000377

AC:

AN:

530276

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

287834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.0014

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.41

.;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.45

.;N

REVEL

Benign

0.022

Sift

Benign

0.21

.;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0

B;B

Vest4

0.062

MutPred

0.20

Loss of phosphorylation at S400 (P = 0.0292);Loss of phosphorylation at S400 (P = 0.0292);

MVP

0.040

ClinPred

0.085

GERP RS

-0.56

Varity_R

0.078

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over