Variant 6-130441137-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001258277.2(TMEM200A):c.715T>A(p.Ser239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TMEM200A
NM_001258277.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.207

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018187523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM200A	NM_001258277.2 link	c.715T>A	p.Ser239Thr	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.715T>A	p.Ser239Thr	missense_variant	3/3	1	NM_001258277.2	ENSP00000296978.3	Q86VY9
TMEM200A	ENST00000392429.1 link	c.715T>A	p.Ser239Thr	missense_variant	2/2	1		ENSP00000376224.1	Q86VY9
TMEM200A	ENST00000545622.5 link	c.715T>A	p.Ser239Thr	missense_variant	2/2	2		ENSP00000438928.1	Q86VY9
TMEM200A	ENST00000617887.4 link	c.715T>A	p.Ser239Thr	missense_variant	2/2	2		ENSP00000480294.1	Q86VY9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250588

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Aug 09, 2021

The c.715T>A (p.S239T) alteration is located in exon 2 (coding exon 1) of the TMEM200A gene. This alteration results from a T to A substitution at nucleotide position 715, causing the serine (S) at amino acid position 239 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

0.062

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.1

DANN

Benign

0.15

DEOGEN2

Benign

0.018

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.38

.;.;T;.

M_CAP

Benign

0.00093

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.090

N;.;N;N

REVEL

Benign

0.047

Sift

Benign

0.41

T;.;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.037

MutPred

0.21

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.043

MPC

0.13

ClinPred

0.055

GERP RS

-2.4

Varity_R

0.025

gMVP

0.13

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