15-89750582-C-T

Position:

chr15-89750582-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018670.4(MESP1):c.650G>A(p.Arg217His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,416,434 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 12 hom., cov: 34)

Exomes 𝑓: 0.00061 ( 9 hom. )

Consequence

MESP1
NM_018670.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.08

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00254637).

BP6

Variant 15-89750582-C-T is Benign according to our data. Variant chr15-89750582-C-T is described in ClinVar as [Benign]. Clinvar id is 1600508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00749 (1141/152276) while in subpopulation AFR AF= 0.0261 (1084/41572). AF 95% confidence interval is 0.0248. There are 12 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP1	NM_018670.4 linkuse as main transcript	c.650G>A	p.Arg217His	missense_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.650G>A	p.Arg217His	missense_variant	1/2	1	NM_018670.4	ENSP00000300057.4		Q9BRJ9
MESP1	ENST00000559894.1 linkuse as main transcript	n.115-355G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1134

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00120

AC:

AN:

27422

Hom.:

AF XY:

0.000951

AC XY:

AN XY:

15766

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000610

AC:

771

AN:

1264158

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

340

AN XY:

617678

show subpopulations

Gnomad4 AFR exome

AF:

0.0262

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000663

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000682

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00749

AC:

1141

AN:

152276

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00438

Hom.:

Bravo

AF:

0.00891

ExAC

AF:

0.00119

AC:

113

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	Jan 13, 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

Apr 01, 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.5

DANN

Uncertain

0.98

DEOGEN2

Benign

0.093

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.46

REVEL

Benign

0.067

Sift

Benign

0.14

Sift4G

Benign

0.62

Polyphen

0.024

Vest4

0.077

MVP

0.19

MPC

0.55

ClinPred

0.0038

GERP RS

0.54

Varity_R

0.025

gMVP

0.11

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