Genetic Variant MESP1:p.Pro229Pro (chr15-89750545-A-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018670.4(MESP1):c.687T>G(p.Pro229Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,481,144 control chromosomes in the GnomAD database, including 296,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33519 hom., cov: 35)

Exomes 𝑓: 0.62 ( 262530 hom. )

Consequence

MESP1
NM_018670.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.22

Variant links:

Genes affected

MESP1 (HGNC:29658): (mesoderm posterior bHLH transcription factor 1) Enables DNA-binding transcription factor activity and transcription cis-regulatory region binding activity. Involved in several processes, including endothelial cell differentiation; heart development; and positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MESP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 15-89750545-A-C is Benign according to our data. Variant chr15-89750545-A-C is described in ClinVar as [Benign]. Clinvar id is 1601156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4 link	c.687T>G	p.Pro229Pro	synonymous_variant	Exon 1 of 2	ENST00000300057.5	NP_061140.1	Q9BRJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP1	ENST00000300057.5 link	c.687T>G	p.Pro229Pro	synonymous_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4		Q9BRJ9
MESP1	ENST00000559894.1 link	n.115-318T>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98630

AN:

151894

Hom.:

33486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.819

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.682

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.647

GnomAD3 exomes

AF:

0.549

AC:

55024

AN:

100312

Hom.:

16041

AF XY:

0.562

AC XY:

31528

AN XY:

56062

show subpopulations

Gnomad AFR exome

AF:

0.801

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.679

Gnomad EAS exome

AF:

0.275

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.577

GnomAD4 exome

AF:

0.623

AC:

828268

AN:

1329138

Hom.:

262530

Cov.:

AF XY:

0.624

AC XY:

407468

AN XY:

652522

show subpopulations

Gnomad4 AFR exome

AF:

0.832

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.709

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.634

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.649

AC:

98713

AN:

152006

Hom.:

33519

Cov.:

AF XY:

0.635

AC XY:

47177

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.820

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.719

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.636

Gnomad4 FIN

AF:

0.470

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.644

Alfa

AF:

0.632

Hom.:

6729

Bravo

AF:

0.659

Asia WGS

AF:

0.486

AC:

1691

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MESP1-related disorder

Benign:1

Nov 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

DANN

Benign

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over