Genetic Variant TMEM200B:p.Ser90Asn (chr1-29121560-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001003682.4(TMEM200B):c.269G>A(p.Ser90Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,503,812 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

TMEM200B
NM_001003682.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.12767583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003682.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM200B	NM_001003682.4	MANE Select	c.269G>A	p.Ser90Asn	missense	Exon 2 of 2	NP_001003682.1	Q69YZ2
	TMEM200B	NM_001171868.2		c.269G>A	p.Ser90Asn	missense	Exon 2 of 2	NP_001165339.1	Q69YZ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM200B	ENST00000521452.2	TSL:1 MANE Select	c.269G>A	p.Ser90Asn	missense	Exon 2 of 2	ENSP00000428459.1	Q69YZ2
TMEM200B	ENST00000420504.2	TSL:1	c.269G>A	p.Ser90Asn	missense	Exon 2 of 2	ENSP00000428544.1	Q69YZ2
TMEM200B	ENST00000870613.1		c.269G>A	p.Ser90Asn	missense	Exon 3 of 3	ENSP00000540672.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

97190

AF XY:

0.0000363

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1352010

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

667548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27574

American (AMR)

AF:

0.00

AC:

AN:

29388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23716

East Asian (EAS)

AF:

0.00

AC:

AN:

32778

South Asian (SAS)

AF:

0.000171

AC:

AN:

75958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33110

Middle Eastern (MID)

AF:

0.000191

AC:

AN:

5228

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067914

Other (OTH)

AF:

0.0000355

AC:

AN:

56344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.0000132

AC:

AN:

151802

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67900

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000386

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.68

REVEL

Benign

0.078

Sift

Benign

0.064

Sift4G

Benign

0.19

Polyphen

0.020

Vest4

0.084

MutPred

0.36

Loss of phosphorylation at S90 (P = 0.0271)

MVP

0.048

MPC

1.5

ClinPred

0.042

GERP RS

2.2

Varity_R

0.093

gMVP

0.30

Mutation Taster

=90/10

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