1-29121548-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001003682.4(TMEM200B):​c.281T>G​(p.Met94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,508,372 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 5 hom. )

Consequence

TMEM200B
NM_001003682.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.898
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008048385).
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM200BNM_001003682.4 linkc.281T>G p.Met94Arg missense_variant Exon 2 of 2 ENST00000521452.2 NP_001003682.1 Q69YZ2
TMEM200BNM_001171868.2 linkc.281T>G p.Met94Arg missense_variant Exon 2 of 2 NP_001165339.1 Q69YZ2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM200BENST00000521452.2 linkc.281T>G p.Met94Arg missense_variant Exon 2 of 2 1 NM_001003682.4 ENSP00000428459.1 Q69YZ2
TMEM200BENST00000420504.2 linkc.281T>G p.Met94Arg missense_variant Exon 2 of 2 1 ENSP00000428544.1 Q69YZ2

Frequencies

GnomAD3 genomes
AF:
0.00142
AC:
216
AN:
151656
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000556
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000831
Gnomad FIN
AF:
0.00267
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00231
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00114
AC:
118
AN:
103874
Hom.:
0
AF XY:
0.00104
AC XY:
61
AN XY:
58510
show subpopulations
Gnomad AFR exome
AF:
0.000668
Gnomad AMR exome
AF:
0.000157
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000605
Gnomad FIN exome
AF:
0.00123
Gnomad NFE exome
AF:
0.00232
Gnomad OTH exome
AF:
0.000613
GnomAD4 exome
AF:
0.00236
AC:
3201
AN:
1356608
Hom.:
5
Cov.:
31
AF XY:
0.00227
AC XY:
1520
AN XY:
669808
show subpopulations
Gnomad4 AFR exome
AF:
0.000283
Gnomad4 AMR exome
AF:
0.000233
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000536
Gnomad4 FIN exome
AF:
0.00187
Gnomad4 NFE exome
AF:
0.00278
Gnomad4 OTH exome
AF:
0.00200
GnomAD4 genome
AF:
0.00142
AC:
215
AN:
151764
Hom.:
0
Cov.:
32
AF XY:
0.00132
AC XY:
98
AN XY:
74192
show subpopulations
Gnomad4 AFR
AF:
0.000555
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000832
Gnomad4 FIN
AF:
0.00267
Gnomad4 NFE
AF:
0.00230
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00115
Hom.:
0
Bravo
AF:
0.00120
ExAC
AF:
0.000352
AC:
18

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.281T>G (p.M94R) alteration is located in exon 2 (coding exon 1) of the TMEM200B gene. This alteration results from a T to G substitution at nucleotide position 281, causing the methionine (M) at amino acid position 94 to be replaced by an arginine (R). 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
0.079
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
9.5
DANN
Benign
0.52
DEOGEN2
Benign
0.0059
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.24
.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.0080
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
0.30
N;N
REVEL
Benign
0.035
Sift
Benign
0.61
T;T
Sift4G
Uncertain
0.024
D;D
Polyphen
0.0050
B;B
Vest4
0.089
MVP
0.030
MPC
1.2
ClinPred
0.0014
T
GERP RS
0.34
Varity_R
0.14
gMVP
0.37

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.

Other links and lift over

dbSNP: rs760009447; hg19: chr1-29448060; COSMIC: COSV100549046; COSMIC: COSV100549046; API