chr1-29121198-C-T

Variant summary

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

The NM_001003682.4(TMEM200B):​c.631G>A​(p.Ala211Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

TMEM200B
NM_001003682.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06
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 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=0.0768176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM200BNM_001003682.4 linkc.631G>A p.Ala211Thr missense_variant Exon 2 of 2 ENST00000521452.2 NP_001003682.1 Q69YZ2
TMEM200BNM_001171868.2 linkc.631G>A p.Ala211Thr 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.631G>A p.Ala211Thr missense_variant Exon 2 of 2 1 NM_001003682.4 ENSP00000428459.1 Q69YZ2
TMEM200BENST00000420504.2 linkc.631G>A p.Ala211Thr missense_variant Exon 2 of 2 1 ENSP00000428544.1 Q69YZ2

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000440
AC:
11
AN:
249792
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135546
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:
0.000279
Gnomad NFE exome
AF:
0.0000444
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000698
AC:
102
AN:
1461138
Hom.:
0
Cov.:
31
AF XY:
0.0000550
AC XY:
40
AN XY:
726894
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:
0.000304
Gnomad4 NFE exome
AF:
0.0000764
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152176
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.631G>A (p.A211T) alteration is located in exon 2 (coding exon 1) of the TMEM200B gene. This alteration results from a G to A substitution at nucleotide position 631, causing the alanine (A) at amino acid position 211 to be replaced by a threonine (T). 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
0.11
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0071
T;T
Eigen
Benign
-0.070
Eigen_PC
Benign
-0.026
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.60
.;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.077
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.64
N;N
REVEL
Benign
0.097
Sift
Uncertain
0.011
D;D
Sift4G
Benign
0.064
T;T
Polyphen
0.98
D;D
Vest4
0.20
MVP
0.13
MPC
1.7
ClinPred
0.16
T
GERP RS
2.8
Varity_R
0.14
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs370894777; hg19: chr1-29447710; COSMIC: COSV58042388; COSMIC: COSV58042388; API