Variant 18-5890866-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395400.1(TMEM200C):c.1198A>C(p.Ser400Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 682,132 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 9 hom. )

Consequence

TMEM200C
NM_001395400.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

MIR3976HG (HGNC:):

MIR3976HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051736534).

BP6

Variant 18-5890866-T-G is Benign according to our data. Variant chr18-5890866-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2648536.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM200C	NM_001395400.1 linkuse as main transcript	c.1198A>C	p.Ser400Arg	missense_variant	2/2	ENST00000383490.3	NP_001382329.1
MIR3976HG	NR_172496.1 linkuse as main transcript	n.1405+1693T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM200C	ENST00000383490.3 linkuse as main transcript	c.1198A>C	p.Ser400Arg	missense_variant	2/2		NM_001395400.1	ENSP00000372982	P1
TMEM200C	ENST00000581347.2 linkuse as main transcript	c.1198A>C	p.Ser400Arg	missense_variant	3/3	5		ENSP00000463375	P1
	ENST00000577694.1 linkuse as main transcript	n.199+1693T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

408

AN:

151750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00345

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00224

AC:

249

AN:

110966

Hom.:

AF XY:

0.00225

AC XY:

138

AN XY:

61410

show subpopulations

Gnomad AFR exome

AF:

0.000299

Gnomad AMR exome

AF:

0.000456

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00107

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.00344

Gnomad OTH exome

AF:

0.00205

GnomAD4 exome

AF:

0.00307

AC:

1630

AN:

530276

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

801

AN XY:

287834

show subpopulations

Gnomad4 AFR exome

AF:

0.000603

Gnomad4 AMR exome

AF:

0.000668

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.0140

Gnomad4 NFE exome

AF:

0.00318

Gnomad4 OTH exome

AF:

0.00309

GnomAD4 genome

AF:

0.00269

AC:

408

AN:

151856

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

231

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.00345

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00172

ExAC

AF:

0.000554

AC:

Asia WGS

AF:

0.000583

AC:

AN:

3446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TMEM200C: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0063

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.51

.;T

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.021

Sift

Benign

0.033

.;D

Sift4G

Uncertain

0.049

D;D

Polyphen

0.14

B;B

Vest4

0.12

MutPred

0.23

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

MVP

0.055

ClinPred

0.027

GERP RS

-0.56

Varity_R

0.17

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over