15-89750563-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018670.4(MESP1):c.669C>G(p.Phe223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,465,286 control chromosomes in the GnomAD database, including 62,707 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5173 hom., cov: 35)

Exomes 𝑓: 0.29 ( 57534 hom. )

Consequence

MESP1
NM_018670.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.256

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039317906).

BP6

Variant 15-89750563-G-C is Benign according to our data. Variant chr15-89750563-G-C is described in ClinVar as Benign. ClinVar VariationId is 1629584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018670.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP1	NM_018670.4	MANE Select	c.669C>G	p.Phe223Leu	missense	Exon 1 of 2	NP_061140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP1	ENST00000300057.5	TSL:1 MANE Select	c.669C>G	p.Phe223Leu	missense	Exon 1 of 2	ENSP00000300057.4
	MESP1	ENST00000559894.1	TSL:2	n.115-336C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38878

AN:

152040

Hom.:

5169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.0954

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.276

GnomAD2 exomes

AF:

0.218

AC:

17159

AN:

78758

AF XY:

0.226

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.0978

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.292

AC:

383049

AN:

1313138

Hom.:

57534

Cov.:

AF XY:

0.293

AC XY:

188451

AN XY:

643374

show subpopulations

African (AFR)

AF:

0.191

AC:

5306

AN:

27804

American (AMR)

AF:

0.170

AC:

4498

AN:

26418

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

6894

AN:

19916

East Asian (EAS)

AF:

0.0878

AC:

3000

AN:

34150

South Asian (SAS)

AF:

0.291

AC:

19651

AN:

67436

European-Finnish (FIN)

AF:

0.258

AC:

8101

AN:

31422

Middle Eastern (MID)

AF:

0.407

AC:

1854

AN:

4550

European-Non Finnish (NFE)

AF:

0.304

AC:

318289

AN:

1047202

Other (OTH)

AF:

0.285

AC:

15456

AN:

54240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15762

31524

47285

63047

78809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10930

21860

32790

43720

54650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.256

AC:

38909

AN:

152148

Hom.:

5173

Cov.:

AF XY:

0.253

AC XY:

18792

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.203

AC:

8416

AN:

41542

American (AMR)

AF:

0.222

AC:

3402

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1215

AN:

3470

East Asian (EAS)

AF:

0.0957

AC:

493

AN:

5150

South Asian (SAS)

AF:

0.291

AC:

1404

AN:

4828

European-Finnish (FIN)

AF:

0.254

AC:

2694

AN:

10590

Middle Eastern (MID)

AF:

0.360

AC:

105

AN:

292

European-Non Finnish (NFE)

AF:

0.301

AC:

20441

AN:

67944

Other (OTH)

AF:

0.276

AC:

585

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1549

3098

4648

6197

7746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.275

Hom.:

1174

Bravo

AF:

0.250

TwinsUK

AF:

0.298

AC:

1104

ALSPAC

AF:

0.291

AC:

1121

ESP6500AA

AF:

0.143

AC:

435

ESP6500EA

AF:

0.220

AC:

1383

ExAC

AF:

0.189

AC:

19070

Asia WGS

AF:

0.179

AC:

621

AN:

3468

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.6

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.11

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.26

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.24

REVEL

Benign

0.062

Sift

Benign

0.23

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.088

MutPred

0.32

Loss of loop (P = 0.0203)

MPC

0.53

ClinPred

0.0025

GERP RS

0.42

Varity_R

0.054

gMVP

0.093

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over