dbSNP rs28377352: MESP1:p.Pro58Pro (chr15-89751058-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_018670.4(MESP1):c.174A>T(p.Pro58Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P58P) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MESP1
NM_018670.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.118

Publications

8 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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4 link	c.174A>T	p.Pro58Pro	synonymous_variant	Exon 1 of 2	ENST00000300057.5	NP_061140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP1	ENST00000300057.5 link	c.174A>T	p.Pro58Pro	synonymous_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4
MESP1	ENST00000559894.1 link	n.80A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1161966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

559844

African (AFR)

AF:

0.00

AC:

AN:

23648

American (AMR)

AF:

0.00

AC:

AN:

9496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15784

East Asian (EAS)

AF:

0.00

AC:

AN:

28030

South Asian (SAS)

AF:

0.00

AC:

AN:

40292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3432

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

966116

Other (OTH)

AF:

0.00

AC:

AN:

47594

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

(source)

DANN

Benign

0.57

PhyloP100

0.12

PromoterAI

0.050

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over