Variant 6-130441771-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.1349T>A(p.Ile450Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,613,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

TMEM200A
NM_001258277.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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=0.06568694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM200A	NM_001258277.2 linkuse as main transcript	c.1349T>A	p.Ile450Asn	missense_variant	3/3	ENST00000296978.4	NP_001245206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM200A	ENST00000296978.4 linkuse as main transcript	c.1349T>A	p.Ile450Asn	missense_variant	3/3	1	NM_001258277.2	ENSP00000296978	P1
TMEM200A	ENST00000392429.1 linkuse as main transcript	c.1349T>A	p.Ile450Asn	missense_variant	2/2	1		ENSP00000376224	P1
TMEM200A	ENST00000545622.5 linkuse as main transcript	c.1349T>A	p.Ile450Asn	missense_variant	2/2	2		ENSP00000438928	P1
TMEM200A	ENST00000617887.4 linkuse as main transcript	c.1349T>A	p.Ile450Asn	missense_variant	2/2	2		ENSP00000480294	P1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000544

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000211

AC:

AN:

250830

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000371

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000423

AC:

619

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000407

AC XY:

296

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000535

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000289

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.00113

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

Apr 21, 2022

The c.1349T>A (p.I450N) 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 1349, causing the isoleucine (I) at amino acid position 450 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

0.082

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.063

T;T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.0083

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.83

.;.;T;.

M_CAP

Benign

0.0036

MetaRNN

Benign

0.066

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

0.79

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;.;N;N

REVEL

Benign

0.035

Sift

Uncertain

0.016

D;.;D;D

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

0.16

B;B;B;B

Vest4

0.29

MVP

0.043

MPC

0.32

ClinPred

0.026

GERP RS

6.0

Varity_R

0.18

gMVP

0.094

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