6-130441012-A-T

Variant summary

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

The NM_001258277.2(TMEM200A):​c.590A>T​(p.Asn197Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TMEM200A
NM_001258277.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66
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]

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=0.07542375).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM200ANM_001258277.2 linkc.590A>T p.Asn197Ile missense_variant 3/3 ENST00000296978.4 NP_001245206.1 Q86VY9A8K2A1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM200AENST00000296978.4 linkc.590A>T p.Asn197Ile missense_variant 3/31 NM_001258277.2 ENSP00000296978.3 Q86VY9
TMEM200AENST00000392429.1 linkc.590A>T p.Asn197Ile missense_variant 2/21 ENSP00000376224.1 Q86VY9
TMEM200AENST00000545622.5 linkc.590A>T p.Asn197Ile missense_variant 2/22 ENSP00000438928.1 Q86VY9
TMEM200AENST00000617887.4 linkc.590A>T p.Asn197Ile missense_variant 2/22 ENSP00000480294.1 Q86VY9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250758
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461688
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 10, 2024The c.590A>T (p.N197I) alteration is located in exon 2 (coding exon 1) of the TMEM200A gene. This alteration results from a A to T substitution at nucleotide position 590, causing the asparagine (N) at amino acid position 197 to be replaced by an isoleucine (I). 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
0.12
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.047
T;T;T;T
Eigen
Benign
-0.045
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.82
.;.;T;.
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.075
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.1
N;.;N;N
REVEL
Benign
0.074
Sift
Benign
0.051
T;.;T;T
Sift4G
Benign
0.29
T;T;T;T
Polyphen
0.0040
B;B;B;B
Vest4
0.39
MutPred
0.20
Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP
0.068
MPC
0.19
ClinPred
0.24
T
GERP RS
5.6
Varity_R
0.12
gMVP
0.40

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: rs768513368; hg19: chr6-130762157; API