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

Variant summary

Our verdict is Likely benign. The variant received -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. 14/21 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. S400R) 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

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395400.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM200C	NM_001395400.1	MANE Select	c.1198A>G	p.Ser400Gly	missense	Exon 2 of 2	NP_001382329.1	A6NKL6
TMEM200C	NM_001080209.3		c.1198A>G	p.Ser400Gly	missense	Exon 3 of 3	NP_001073678.1	A6NKL6
MIR3976HG	NR_172496.1		n.1405+1693T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM200C	ENST00000383490.3	TSL:6 MANE Select	c.1198A>G	p.Ser400Gly	missense	Exon 2 of 2	ENSP00000372982.2	A6NKL6
TMEM200C	ENST00000581347.2	TSL:5	c.1198A>G	p.Ser400Gly	missense	Exon 3 of 3	ENSP00000463375.1	A6NKL6
TMEM200C	ENST00000930047.1		c.1198A>G	p.Ser400Gly	missense	Exon 2 of 2	ENSP00000600106.1

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

African (AFR)

AF:

0.00

AC:

AN:

13268

American (AMR)

AF:

0.00

AC:

AN:

32914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19402

East Asian (EAS)

AF:

0.00

AC:

AN:

29742

South Asian (SAS)

AF:

0.00

AC:

AN:

60774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3238

European-Non Finnish (NFE)

AF:

0.00000649

AC:

AN:

308068

Other (OTH)

AF:

0.00

AC:

AN:

29812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67886

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.41

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.39

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.45

REVEL

Benign

0.022

Sift

Benign

0.21

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.062

MutPred

0.20

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over