6-130440477-T-C

Variant summary

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

The NM_001258277.2(TMEM200A):ā€‹c.55T>Cā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

TMEM200A
NM_001258277.2 missense

Scores

4
5
10

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]

Genome browser will be placed here

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
TMEM200ANM_001258277.2 linkuse as main transcriptc.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 Appris UniProt
TMEM200AENST00000296978.4 linkuse as main transcriptc.55T>C p.Ser19Pro missense_variant 3/31 NM_001258277.2 ENSP00000296978.3 Q86VY9
TMEM200AENST00000392429.1 linkuse as main transcriptc.55T>C p.Ser19Pro missense_variant 2/21 ENSP00000376224.1 Q86VY9
TMEM200AENST00000545622.5 linkuse as main transcriptc.55T>C p.Ser19Pro missense_variant 2/22 ENSP00000438928.1 Q86VY9
TMEM200AENST00000617887.4 linkuse as main transcriptc.55T>C p.Ser19Pro missense_variant 2/22 ENSP00000480294.1 Q86VY9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1459778
Hom.:
0
Cov.:
32
AF XY:
0.00000689
AC XY:
5
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.:
32

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 GeneticsMay 17, 2023The 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
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
27
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
D
LIST_S2
Benign
0.78
.;.;T;.
M_CAP
Benign
0.0054
T
MetaRNN
Pathogenic
0.76
D;D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.4
L;L;L;L
PrimateAI
Uncertain
0.70
T
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
D
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.

Other links and lift over

hg19: chr6-130761622; API