chr12-57036339-G-G

Variant names:

• chr12-57036339-G-G
• NM_005379.4:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005379.4(MYO1A):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO1A NM_005379.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 0 publications found

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

MYO1A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1A	NM_005379.4	MANE Select	c.		exon_region	Exon 22 of 28	NP_005370.1	Q9UBC5
	MYO1A	NM_001256041.2		c.		exon_region	Exon 23 of 29	NP_001242970.1	Q9UBC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1A	ENST00000300119.8	TSL:1 MANE Select	c.		exon_region	Exon 22 of 28	ENSP00000300119.3	Q9UBC5
	MYO1A	ENST00000442789.6	TSL:1	c.		exon_region	Exon 23 of 29	ENSP00000393392.2	Q9UBC5
	MYO1A	ENST00000907120.1		c.		exon_region	Exon 22 of 28	ENSP00000577179.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.96

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-57430123;