rs6496598

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.157G>C(p.Ala53Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,315,716 control chromosomes in the GnomAD database, including 58,559 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9195 hom., cov: 34)

Exomes 𝑓: 0.28 ( 49364 hom. )

Consequence

MESP1
NM_018670.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

Publications

19 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=2.1452904E-6).

BP6

Variant 15-89751075-C-G is Benign according to our data. Variant chr15-89751075-C-G is described in ClinVar as Benign. ClinVar VariationId is 1598905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4 link	c.157G>C	p.Ala53Pro	missense_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.157G>C	p.Ala53Pro	missense_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4		Q9BRJ9
MESP1	ENST00000559894.1 link	n.63G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49526

AN:

151600

Hom.:

9197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.0896

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.321

GnomAD2 exomes

AF:

0.338

AC:

6783

AN:

20060

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.761

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.361

GnomAD4 exome

AF:

0.281

AC:

327564

AN:

1164012

Hom.:

49364

Cov.:

AF XY:

0.284

AC XY:

159051

AN XY:

559250

show subpopulations

African (AFR)

AF:

0.544

AC:

12962

AN:

23828

American (AMR)

AF:

0.200

AC:

2093

AN:

10452

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

5344

AN:

15670

East Asian (EAS)

AF:

0.0792

AC:

2248

AN:

28386

South Asian (SAS)

AF:

0.384

AC:

14577

AN:

37982

European-Finnish (FIN)

AF:

0.244

AC:

6668

AN:

27300

Middle Eastern (MID)

AF:

0.421

AC:

1397

AN:

3318

European-Non Finnish (NFE)

AF:

0.277

AC:

268488

AN:

969598

Other (OTH)

AF:

0.290

AC:

13787

AN:

47478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

13353

26707

40060

53414

66767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9962

19924

29886

39848

49810

<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:

0.327

AC:

49550

AN:

151704

Hom.:

9195

Cov.:

AF XY:

0.320

AC XY:

23724

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.511

AC:

21168

AN:

41406

American (AMR)

AF:

0.233

AC:

3561

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

1110

AN:

3466

East Asian (EAS)

AF:

0.0897

AC:

460

AN:

5128

South Asian (SAS)

AF:

0.302

AC:

1455

AN:

4812

European-Finnish (FIN)

AF:

0.232

AC:

2445

AN:

10550

Middle Eastern (MID)

AF:

0.397

AC:

116

AN:

292

European-Non Finnish (NFE)

AF:

0.272

AC:

18430

AN:

67778

Other (OTH)

AF:

0.322

AC:

676

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1620

3239

4859

6478

8098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.541

Hom.:

2777

Bravo

AF:

0.601

ExAC

AF:

0.289

AC:

23815

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.7

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.080

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000021

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

PhyloP100

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

1.6

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.025

MPC

0.58

ClinPred

0.0053

GERP RS

2.5

PromoterAI

-0.0034

Neutral

(source)

Varity_R

0.065

gMVP

0.35

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over