Genetic Variant TMEM200B:p.Glu100Gln (chr1-29121531-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003682.4(TMEM200B):c.298G>C(p.Glu100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000037 in 1,351,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TMEM200B
NM_001003682.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

TMEM200B (HGNC:33785): (transmembrane protein 200B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM200B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24546418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200B	NM_001003682.4 link	c.298G>C	p.Glu100Gln	missense_variant	Exon 2 of 2	ENST00000521452.2	NP_001003682.1	Q69YZ2
TMEM200B	NM_001171868.2 link	c.298G>C	p.Glu100Gln	missense_variant	Exon 2 of 2		NP_001165339.1	Q69YZ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM200B	ENST00000521452.2 link	c.298G>C	p.Glu100Gln	missense_variant	Exon 2 of 2	1	NM_001003682.4	ENSP00000428459.1		Q69YZ2
TMEM200B	ENST00000420504.2 link	c.298G>C	p.Glu100Gln	missense_variant	Exon 2 of 2	1		ENSP00000428544.1		Q69YZ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000988

AC:

AN:

101168

Hom.:

AF XY:

0.0000176

AC XY:

AN XY:

56742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000370

AC:

AN:

1351322

Hom.:

Cov.:

AF XY:

0.00000451

AC XY:

AN XY:

665828

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:

0.00000469

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298G>C (p.E100Q) alteration is located in exon 2 (coding exon 1) of the TMEM200B gene. This alteration results from a G to C substitution at nucleotide position 298, causing the glutamic acid (E) at amino acid position 100 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0063

T;T

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.52

.;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

L;L

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.099

Sift

Benign

0.28

T;T

Sift4G

Benign

0.095

T;T

Polyphen

0.94

P;P

Vest4

0.11

MutPred

0.64

Gain of MoRF binding (P = 0.0522);Gain of MoRF binding (P = 0.0522);

MVP

0.12

MPC

0.93

ClinPred

0.23

GERP RS

1.8

Varity_R

0.13

gMVP

0.45

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