Variant chr6-130440477-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001258277.2(TMEM200A):c.55T>C(p.Ser19Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TMEM200A
NM_001258277.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM200A	NM_001258277.2 linkuse as main transcript	c.55T>C	p.Ser19Pro	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 linkuse as main transcript	c.55T>C	p.Ser19Pro	missense_variant	3/3	1	NM_001258277.2	ENSP00000296978.3	Q86VY9
TMEM200A	ENST00000392429.1 linkuse as main transcript	c.55T>C	p.Ser19Pro	missense_variant	2/2	1		ENSP00000376224.1	Q86VY9
TMEM200A	ENST00000545622.5 linkuse as main transcript	c.55T>C	p.Ser19Pro	missense_variant	2/2	2		ENSP00000438928.1	Q86VY9
TMEM200A	ENST00000617887.4 linkuse as main transcript	c.55T>C	p.Ser19Pro	missense_variant	2/2	2		ENSP00000480294.1	Q86VY9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459778

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725990

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 17, 2023

The c.55T>C (p.S19P) alteration is located in exon 2 (coding exon 1) of the TMEM200A gene. This alteration results from a T to C substitution at nucleotide position 55, causing the serine (S) at amino acid position 19 to be replaced by a proline (P). 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

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;T;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

.;.;T;.

M_CAP

Benign

0.0054

MetaRNN

Pathogenic

0.76

D;D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.4

L;L;L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

2.4

N;.;N;N

REVEL

Benign

0.28

Sift

Benign

0.36

T;.;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.75

MutPred

0.59

Loss of phosphorylation at S19 (P = 0.0223);Loss of phosphorylation at S19 (P = 0.0223);Loss of phosphorylation at S19 (P = 0.0223);Loss of phosphorylation at S19 (P = 0.0223);

MVP

0.11

MPC

0.71

ClinPred

0.95

GERP RS

5.3

Varity_R

0.28

gMVP

0.83

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over