chr15-89751065-G-GCGGGGCTCGGCA

Position:

• chr15-89751065-G-GCGGGGCTCGGCA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_018670.4(MESP1):​c.166_167insTGCCGAGCCCCG​(p.Pro55_Ala56insValProSerPro) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,239,364 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00019 (4 hom.)
• Consequence: MESP1 NM_018670.4 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B: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 Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018670.4.
• BP6: Variant 15-89751065-G-GCGGGGCTCGGCA is Benign according to our data. Variant chr15-89751065-G-GCGGGGCTCGGCA is described in ClinVar as [Benign]. Clinvar id is 1649722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP1	NM_018670.4	c.166_167insTGCCGAGCCCCG	p.Pro55_Ala56insValProSerPro	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_167insTGCCGAGCCCCG	p.Pro55_Ala56insValProSerPro	inframe_insertion	1/2	1	NM_018670.4	ENSP00000300057	P1
MESP1	ENST00000559894.1	n.72_73insTGCCGAGCCCCG		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.000581 AC: 48 AN: 82682 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000254

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000269

Gnomad OTH AF: 0.000858

GnomAD3 exomes AF: 0.000156 AC: 2 AN: 12840 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7410

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 SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000188 AC: 218 AN: 1156640 Hom.: 4 Cov.: 56 AF XY: 0.000221 AC XY: 123 AN XY: 556614

Gnomad4 AFR exome AF: 0.000211

Gnomad4 AMR exome AF: 0.000102

Gnomad4 ASJ exome AF: 0.000190

Gnomad4 EAS exome AF: 0.000178

Gnomad4 SAS exome AF: 0.00306

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000614

Gnomad4 OTH exome AF: 0.000465

GnomAD4 genome AF: 0.000592 AC: 49 AN: 82724 Hom.: 0 Cov.: 24 AF XY: 0.000729 AC XY: 30 AN XY: 41158

Gnomad4 AFR AF: 0.000374

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000255

Gnomad4 SAS AF: 0.0115

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000269

Gnomad4 OTH AF: 0.00252

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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;