Genetic Variant TMEM200A:p.Thr209Met (chr6-130441048-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001258277.2(TMEM200A):c.626C>T(p.Thr209Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. T209R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

TMEM200A
NM_001258277.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.82

Publications

0 publications found

Variant links:

Genes affected

TMEM200A (HGNC:21075): (transmembrane protein 200A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM200A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11592826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258277.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM200A	NM_001258277.2	MANE Select	c.626C>T	p.Thr209Met	missense	Exon 3 of 3	NP_001245206.1	Q86VY9
TMEM200A	NM_001258276.2		c.626C>T	p.Thr209Met	missense	Exon 2 of 2	NP_001245205.1	Q86VY9
TMEM200A	NM_001258278.2		c.626C>T	p.Thr209Met	missense	Exon 2 of 2	NP_001245207.1	Q86VY9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM200A	ENST00000296978.4	TSL:1 MANE Select	c.626C>T	p.Thr209Met	missense	Exon 3 of 3	ENSP00000296978.3	Q86VY9
TMEM200A	ENST00000392429.1	TSL:1	c.626C>T	p.Thr209Met	missense	Exon 2 of 2	ENSP00000376224.1	Q86VY9
TMEM200A	ENST00000545622.5	TSL:2	c.626C>T	p.Thr209Met	missense	Exon 2 of 2	ENSP00000438928.1	Q86VY9

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000639

AC:

AN:

250426

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461596

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.0000895

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39592

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111918

Other (OTH)

AF:

0.0000828

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000565

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0065

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.0

PhyloP100

4.8

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.74

REVEL

Benign

0.10

Sift

Uncertain

0.017

Sift4G

Benign

0.13

Polyphen

0.40

Vest4

0.38

MutPred

0.43

Gain of MoRF binding (P = 0.0651)

MVP

0.068

MPC

0.32

ClinPred

0.034

GERP RS

4.7

Varity_R

0.084

gMVP

0.38

Mutation Taster

=69/31

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

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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