Variant chr15-89751058-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018670.4(MESP1):c.174A>C(p.Pro58Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,302,904 control chromosomes in the GnomAD database, including 51,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6785 hom., cov: 34)

Exomes 𝑓: 0.27 ( 44479 hom. )

Consequence

MESP1
NM_018670.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.118

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:

MESP1 (HGNC:):

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=-0.83).

BP6

Variant 15-89751058-T-G is Benign according to our data. Variant chr15-89751058-T-G is described in ClinVar as [Benign]. Clinvar id is 1600319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP1	NM_018670.4 linkuse as main transcript	c.174A>C	p.Pro58Pro	synonymous_variant	1/2	ENST00000300057.5	NP_061140.1	Q9BRJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MESP1	ENST00000300057.5 linkuse as main transcript	c.174A>C	p.Pro58Pro	synonymous_variant	1/2	1	NM_018670.4	ENSP00000300057.4		Q9BRJ9
MESP1	ENST00000559894.1 linkuse as main transcript	n.80A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44157

AN:

150992

Hom.:

6771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.0448

AC:

515

AN:

11500

Hom.:

AF XY:

0.0480

AC XY:

314

AN XY:

6544

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.00883

Gnomad ASJ exome

AF:

0.00862

Gnomad EAS exome

AF:

0.00871

Gnomad SAS exome

AF:

0.0358

Gnomad FIN exome

AF:

0.0434

Gnomad NFE exome

AF:

0.0559

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.272

AC:

313567

AN:

1151804

Hom.:

44479

Cov.:

AF XY:

0.270

AC XY:

149641

AN XY:

554192

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.293

AC:

44203

AN:

151100

Hom.:

6785

Cov.:

AF XY:

0.286

AC XY:

21139

AN XY:

73872

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.271

Hom.:

691

Bravo

AF:

0.294

Asia WGS

AF:

0.219

AC:

760

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MESP1-related disorder

Benign:1

Benign, no assertion criteria provided

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.5

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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