17-1467629-C-G

Variant names:

• chr17-1467629-C-G
• rs115083063
• NM_001080779.2:c.2968-52G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080779.2(MYO1C):​c.2968-52G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,405,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 0 publications found

Genes affected

MYO1C (HGNC:7597): (myosin IC) This gene encodes a member of the unconventional myosin protein family, which are actin-based molecular motors. The protein is found in the cytoplasm, and one isoform with a unique N-terminus is also found in the nucleus. The nuclear isoform associates with RNA polymerase I and II and functions in transcription initiation. The mouse ortholog of this protein also functions in intracellular vesicle transport to the plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. The related gene myosin IE has been referred to as myosin IC in the literature, but it is a distinct locus on chromosome 19. [provided by RefSeq, Jul 2008]

MYO1C Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080779.2. 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
	MYO1C	NM_001080779.2	MANE Select	c.2968-52G>C		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.2911-52G>C		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.2896-52G>C		intron	N/A	NP_001350784.1	F5H6E2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1C	ENST00000648651.1	MANE Select	c.2968-52G>C		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.2962-52G>C		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.2962-52G>C		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1405758 Hom.: 0 Cov.: 27 AF XY: 0.00000285 AC XY: 2 AN XY: 701614

African (AFR) AF: 0.00 AC: 0 AN: 32448

American (AMR) AF: 0.00 AC: 0 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 39260

South Asian (SAS) AF: 0.00 AC: 0 AN: 84802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44264

Middle Eastern (MID) AF: 0.000212 AC: 1 AN: 4708

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1071788

Other (OTH) AF: 0.0000171 AC: 1 AN: 58608

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.56
PhyloP100		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs115083063; hg19: chr17-1370923;