Genetic Variant NM_002402.4:c.281T>C (chr7-130497955-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002402.4(MEST):c.281T>C(p.Leu94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MEST
NM_002402.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Variant links:

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]

MEST links:

ENSG00000270823 (HGNC:):

ENSG00000270823 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18246111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEST	NM_002402.4 link	c.281T>C	p.Leu94Ser	missense_variant	Exon 4 of 12	ENST00000223215.10	NP_002393.2	Q5EB52-1A0A024R768

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10 link	c.281T>C	p.Leu94Ser	missense_variant	Exon 4 of 12	1	NM_002402.4	ENSP00000223215.4		Q5EB52-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000398

AC:

AN:

251482

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.00000137

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0053

.;.;.;.;.;T;.;T;T;.;.;.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

.;.;.;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.13

.;.;.;.;.;.;.;.;N;.;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.9

N;N;N;N;N;N;N;N;N;N;.;N;N

REVEL

Benign

0.14

Sift

Benign

0.73

T;T;T;T;T;T;T;T;T;T;.;T;T

Sift4G

Benign

0.77

T;T;T;T;T;T;T;T;T;T;.;T;T

Polyphen

0.0, 0.0030, 0.013

.;B;B;B;.;.;.;.;B;B;.;.;.

Vest4

0.40

MutPred

0.37

.;.;.;.;.;.;.;.;Loss of stability (P = 0.0215);Loss of stability (P = 0.0215);.;.;.;

MVP

0.25

MPC

1.2

ClinPred

0.21

GERP RS

2.7

Varity_R

0.043

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over