Variant 6-130441012-A-T details in Genebe, Genetics Data Aggregator

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

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]

TMEM200A links:

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
TMEM200A	NM_001258277.2 link	c.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	UniProt
TMEM200A	ENST00000296978.4 link	c.590A>T	p.Asn197Ile	missense_variant	3/3	1	NM_001258277.2	ENSP00000296978.3	Q86VY9
TMEM200A	ENST00000392429.1 link	c.590A>T	p.Asn197Ile	missense_variant	2/2	1		ENSP00000376224.1	Q86VY9
TMEM200A	ENST00000545622.5 link	c.590A>T	p.Asn197Ile	missense_variant	2/2	2		ENSP00000438928.1	Q86VY9
TMEM200A	ENST00000617887.4 link	c.590A>T	p.Asn197Ile	missense_variant	2/2	2		ENSP00000480294.1	Q86VY9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250758

Hom.:

AF XY:

0.0000221

AC XY:

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:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The 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

BayesDel_noAF

Benign

-0.31

CADD

Benign

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

LIST_S2

Benign

0.82

.;.;T;.

M_CAP

Benign

0.0031

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N

PrimateAI

Benign

0.42

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over