Variant 7-130498199-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_002402.4(MEST):c.400C>T(p.Leu134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,614,156 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0082 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 35 hom. )

Consequence

MEST
NM_002402.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.518

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=0.518 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00822 (1252/152284) while in subpopulation AFR AF= 0.0216 (898/41560). AF 95% confidence interval is 0.0204. There are 9 homozygotes in gnomad4. There are 581 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1252 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEST	NM_002402.4 linkuse as main transcript	c.400C>T	p.Leu134=	synonymous_variant	5/12	ENST00000223215.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEST	ENST00000223215.10 linkuse as main transcript	c.400C>T	p.Leu134=	synonymous_variant	5/12	1	NM_002402.4		Q5EB52-1
	ENST00000604666.1 linkuse as main transcript	n.229G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00821

AC:

1249

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00395

AC:

992

AN:

251390

Hom.:

AF XY:

0.00354

AC XY:

481

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0213

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00241

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00272

AC:

3982

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

1909

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.00789

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.00822

AC:

1252

AN:

152284

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

581

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00503

Hom.:

Bravo

AF:

0.00979

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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