chr12-80717083-GCCAGTTCTCA-G

Variant names:

• chr12-80717083-GCCAGTTCTCA-G
• rs1555216163
• NM_005593.3:c.23_32delAGTTCTCACC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_005593.3(MYF5):​c.23_32delAGTTCTCACC​(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 NM_005593.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 7.48
• Publications: 1 publications found

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]

MYF5 Gene-Disease associations (from GenCC):

• ophthalmoplegia, external, with rib and vertebral anomalies

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 523663.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005593.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYF5	NM_005593.3	MANE Select	c.23_32delAGTTCTCACC	p.Gln8LeufsTer86	frameshift	Exon 1 of 3	NP_005584.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYF5	ENST00000228644.4	TSL:1 MANE Select	c.23_32delAGTTCTCACC	p.Gln8LeufsTer86	frameshift	Exon 1 of 3	ENSP00000228644.3

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

Engle Laboratory, Boston Children's Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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

Oct 26, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5
Mutation Taster		=8/192	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1555216163; hg19: chr12-81110862;