Variant 15-89750706-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_018670.4(MESP1):c.526A>T(p.Thr176Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,381,292 control chromosomes in the GnomAD database, including 2 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

MESP1
NM_018670.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0420

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040586293).

BP6

Variant 15-89750706-T-A is Benign according to our data. Variant chr15-89750706-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1633924.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MESP1	NM_018670.4 linkuse as main transcript	c.526A>T	p.Thr176Ser	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.526A>T	p.Thr176Ser	missense_variant	1/2	1	NM_018670.4	P1
MESP1	ENST00000559894.1 linkuse as main transcript	n.114+318A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000521

AC:

AN:

38352

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

22148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00607

Gnomad SAS exome

AF:

0.000285

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000195

AC:

240

AN:

1229076

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

110

AN XY:

596320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00589

Gnomad4 SAS exome

AF:

0.000947

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000356

GnomAD4 genome

AF:

0.000374

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0101

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000514

ExAC

AF:

0.000279

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

Cadd

Benign

9.7

Dann

Benign

0.89

DEOGEN2

Benign

0.13

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.44

REVEL

Benign

0.21

Sift

Benign

0.37

Sift4G

Benign

0.90

Polyphen

0.96

Vest4

0.10

MutPred

0.13

Gain of phosphorylation at T176 (P = 0.0783);

MVP

0.48

MPC

0.42

ClinPred

0.045

GERP RS

1.1

Varity_R

0.031

gMVP

0.15

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