Genetic Variant MESP1:p.Arg217Leu (chr15-89750582-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018670.4(MESP1):c.650G>T(p.Arg217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,264,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217H) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

MESP1
NM_018670.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

0 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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

MESP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0705705).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP1	NM_018670.4	MANE Select	c.650G>T	p.Arg217Leu	missense	Exon 1 of 2	NP_061140.1	Q9BRJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP1	ENST00000300057.5	TSL:1 MANE Select	c.650G>T	p.Arg217Leu	missense	Exon 1 of 2	ENSP00000300057.4	Q9BRJ9
	MESP1	ENST00000559894.1	TSL:2	n.115-355G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

27422

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.91e-7

AC:

AN:

1264162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

617682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24846

American (AMR)

AF:

0.00

AC:

AN:

17328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18422

East Asian (EAS)

AF:

0.0000336

AC:

AN:

29770

South Asian (SAS)

AF:

0.00

AC:

AN:

60362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4164

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026596

Other (OTH)

AF:

0.00

AC:

AN:

52230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.5

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.085

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PhyloP100

-2.1

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.11

REVEL

Benign

0.093

Sift

Benign

0.15

Sift4G

Benign

0.75

Polyphen

0.031

Vest4

0.096

MutPred

0.21

Loss of glycosylation at P220 (P = 0.1099)

MVP

0.10

MPC

0.55

ClinPred

0.054

GERP RS

0.54

Varity_R

0.061

gMVP

0.14

Mutation Taster

=98/2

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over