7-130499898-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_002402.4(MEST):c.559C>T(p.Pro187Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MEST
NM_002402.4 missense
NM_002402.4 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
MEST (HGNC:7028): (mesoderm specific transcript) This gene encodes a member of the alpha/beta hydrolase superfamily. It is imprinted, exhibiting preferential expression from the paternal allele in fetal tissues, and isoform-specific imprinting in lymphocytes. The loss of imprinting of this gene has been linked to certain types of cancer and may be due to promotor switching. The encoded protein may play a role in development. Alternatively spliced transcript variants encoding multiple isoforms have been identified for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3 and 4, and the long arm of chromosomes 6 and 15. [provided by RefSeq, Dec 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-130499898-C-T is Pathogenic according to our data. Variant chr7-130499898-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208394.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-130499898-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEST | NM_002402.4 | c.559C>T | p.Pro187Ser | missense_variant | Exon 7 of 12 | ENST00000223215.10 | NP_002393.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250428 AF XY: 0.00000739 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250428
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460418Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726560 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460418
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726560
Gnomad4 AFR exome
AF:
AC:
0
AN:
33350
Gnomad4 AMR exome
AF:
AC:
0
AN:
44456
Gnomad4 ASJ exome
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AC:
0
AN:
26106
Gnomad4 EAS exome
AF:
AC:
0
AN:
39676
Gnomad4 SAS exome
AF:
AC:
0
AN:
86028
Gnomad4 FIN exome
AF:
AC:
0
AN:
53408
Gnomad4 NFE exome
AF:
AC:
0
AN:
1111316
Gnomad4 Remaining exome
AF:
AC:
1
AN:
60318
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Childhood-onset schizophrenia Pathogenic:1
Jan 01, 2014
Dr. Guy Rouleau's laboratory, McGill University
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:research
COS with PDD NOS, Asperger's Disorder, Separation Anxiety Disorder -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;.;T;T;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;.;.;D;D;D;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;.;.;.;.;.;M;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;.;.;.;.
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;.;.;.;.
Sift4G
Uncertain
D;D;D;D;D;D;D;.;.;.;D
Polyphen
0.71, 0.57
.;P;P;P;.;.;P;.;.;.;.
Vest4
MutPred
0.59
.;.;.;.;.;.;Loss of helix (P = 0.079);.;.;.;.;
MVP
MPC
1.5
ClinPred
D
GERP RS
Varity_R
gMVP
Mutation Taster
=76/24
disease causing (ClinVar)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at