chr12-80717083-GCCAGTTCTCA-G

Position:

• chr12-80717083-GCCAGTTCTCA-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000228644.4(MYF5):​c.23_32del​(p.Gln8LeufsTer86) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYF5 ENST00000228644.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 7.48

Genes affected

MYF5 (HGNC:7565): (myogenic factor 5) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to contribute to E-box binding activity. Predicted to be involved in several processes, including muscle cell fate commitment; positive regulation of cell differentiation; and skeletal muscle cell differentiation. Predicted to act upstream of or within several processes, including animal organ development; regulation of cell-matrix adhesion; and somitogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-80717083-GCCAGTTCTCA-G is Pathogenic according to our data. Variant chr12-80717083-GCCAGTTCTCA-G is described in ClinVar as [Pathogenic]. Clinvar id is 523663.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYF5	NM_005593.3	c.23_32del	p.Gln8LeufsTer86	frameshift_variant	1/3	ENST00000228644.4	NP_005584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYF5	ENST00000228644.4	c.23_32del	p.Gln8LeufsTer86	frameshift_variant	1/3	1	NM_005593.3	ENSP00000228644	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Scoliosis;C0162292:External ophthalmoplegia;C1842083:Abnormal rib morphology Pathogenic:1

Pathogenic, no assertion criteria provided

research

Engle Laboratory, Boston Children's Hospital

-

- -

Ophthalmoplegia, external, with rib and vertebral anomalies Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 26, 2018

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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: rs1555216163; hg19: chr12-81110862;