rs6496598

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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:2

Conservation

PhyloP100: 1.03

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 -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 id 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/exons	MANE	UniProt
MESP1	NM_018670.4 linkuse as main transcript	c.157G>C	p.Ala53Pro	missense_variant	1/2	ENST00000300057.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MESP1	ENST00000300057.5 linkuse as main transcript	c.157G>C	p.Ala53Pro	missense_variant	1/2	1	NM_018670.4	P1
MESP1	ENST00000559894.1 linkuse as main transcript	n.63G>C		non_coding_transcript_exon_variant	1/2	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

GnomAD3 exomes

AF:

0.338

AC:

6783

AN:

20060

Hom.:

1440

AF XY:

0.345

AC XY:

3939

AN XY:

11412

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 SAS exome

AF:

0.429

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

Gnomad4 AFR exome

AF:

0.544

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.0792

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.327

AC:

49550

AN:

151704

Hom.:

9195

Cov.:

AF XY:

0.320

AC XY:

23724

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.0897

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.541

Hom.:

2777

Bravo

AF:

0.601

ExAC

AF:

0.289

AC:

23815

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MESP1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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

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

MutationTaster

Benign

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

Varity_R

0.065

gMVP

0.35

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