chr1-29121560-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.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. 13/20 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

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44
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=0.12767583).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM200BNM_001003682.4 linkc.269G>A p.Ser90Asn missense_variant Exon 2 of 2 ENST00000521452.2 NP_001003682.1 Q69YZ2
TMEM200BNM_001171868.2 linkc.269G>A p.Ser90Asn 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.269G>A p.Ser90Asn missense_variant Exon 2 of 2 1 NM_001003682.4 ENSP00000428459.1 Q69YZ2
TMEM200BENST00000420504.2 linkc.269G>A p.Ser90Asn missense_variant Exon 2 of 2 1 ENSP00000428544.1 Q69YZ2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151802
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000206
AC:
2
AN:
97190
Hom.:
0
AF XY:
0.0000363
AC XY:
2
AN XY:
55154
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:
0.000104
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000118
AC:
16
AN:
1352010
Hom.:
1
Cov.:
31
AF XY:
0.0000165
AC XY:
11
AN XY:
667548
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:
0.000171
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000355
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151802
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74152
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000386
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.269G>A (p.S90N) 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 269, causing the serine (S) at amino acid position 90 to be replaced by an asparagine (N). 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
0.23
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
18
DANN
Benign
0.90
DEOGEN2
Benign
0.0045
T;T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.44
.;T
M_CAP
Pathogenic
0.46
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.68
N;N
REVEL
Benign
0.078
Sift
Benign
0.064
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.020
B;B
Vest4
0.084
MutPred
0.36
Loss of phosphorylation at S90 (P = 0.0271);Loss of phosphorylation at S90 (P = 0.0271);
MVP
0.048
MPC
1.5
ClinPred
0.042
T
GERP RS
2.2
Varity_R
0.093
gMVP
0.30

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: rs768573346; hg19: chr1-29448072; API