Genetic Variant MESP1:p.Pro219Pro (chr15-89750575-C-A) – 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.657G>T(p.Pro219Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,433,414 control chromosomes in the GnomAD database, including 6,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1181 hom., cov: 35)

Exomes 𝑓: 0.080 ( 4869 hom. )

Consequence

MESP1
NM_018670.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 15-89750575-C-A is Benign according to our data. Variant chr15-89750575-C-A is described in ClinVar as [Benign]. Clinvar id is 1561757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4 link	c.657G>T	p.Pro219Pro	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.657G>T	p.Pro219Pro	synonymous_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4		Q9BRJ9
MESP1	ENST00000559894.1 link	n.115-348G>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16803

AN:

152120

Hom.:

1175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0857

Gnomad FIN

AF:

0.0763

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0695

Gnomad OTH

AF:

0.0979

GnomAD3 exomes

AF:

0.196

AC:

8155

AN:

41712

Hom.:

750

AF XY:

0.179

AC XY:

4201

AN XY:

23472

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.257

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.0803

AC:

102911

AN:

1281186

Hom.:

4869

Cov.:

AF XY:

0.0800

AC XY:

50166

AN XY:

626728

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.0283

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.0912

Gnomad4 FIN exome

AF:

0.0871

Gnomad4 NFE exome

AF:

0.0712

Gnomad4 OTH exome

AF:

0.0798

GnomAD4 genome

AF:

0.111

AC:

16827

AN:

152228

Hom.:

1181

Cov.:

AF XY:

0.110

AC XY:

8153

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0854

Gnomad4 FIN

AF:

0.0763

Gnomad4 NFE

AF:

0.0695

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.0345

Hom.:

Bravo

AF:

0.121

Asia WGS

AF:

0.119

AC:

413

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 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MESP1-related disorder

Benign:1

Oct 28, 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

-0.58

CADD

Benign

3.6

DANN

Benign

0.76

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