chr15-89751065-G-GCGGGGCTCGGCACGGGGCTCGGCA

Position:

• chr15-89751065-G-GCGGGGCTCGGCACGGGGCTCGGCA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_018670.4(MESP1):​c.166_167insTGCCGAGCCCCGTGCCGAGCCCCG​(p.Pro55_Ala56insValProSerProValProSerPro) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MESP1 NM_018670.4 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018670.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP1	NM_018670.4	c.166_167insTGCCGAGCCCCGTGCCGAGCCCCG	p.Pro55_Ala56insValProSerProValProSerPro	inframe_insertion	1/2	ENST00000300057.5	NP_061140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MESP1	ENST00000300057.5	c.166_167insTGCCGAGCCCCGTGCCGAGCCCCG	p.Pro55_Ala56insValProSerProValProSerPro	inframe_insertion	1/2	1	NM_018670.4	ENSP00000300057	P1
MESP1	ENST00000559894.1	n.72_73insTGCCGAGCCCCGTGCCGAGCCCCG		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 15, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with MESP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.166_167insTGCCGAGCCCCGTGCCGAGCCCCG, results in the insertion of 8 amino acid(s) of the MESP1 protein (p.Pro55_Ala56insValProSerProValProSerPro), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3841586; hg19: chr15-90294296;