NM_001080779.2:c.2968-3dupC

Variant names:

• chr17-1467579-T-TG
• rs538792546
• NM_001080779.2:c.2968-3dupC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001080779.2(MYO1C):​c.2968-3dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,612,582 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (1 hom.)
• Consequence: MYO1C NM_001080779.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.50
• Publications: 1 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 -6 ACMG points.

• BP6: Variant 17-1467579-T-TG is Benign according to our data. Variant chr17-1467579-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1291838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 168 AD gene.

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.2968-3dupC		splice_region intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.2911-3dupC		splice_region intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.2896-3dupC		splice_region 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.2968-3_2968-2insC		splice_region intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.2962-3_2962-2insC		splice_region intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.2962-3_2962-2insC		splice_region intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 151702 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00110 AC: 275 AN: 249610 AF XY: 0.00125

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00867

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.0000960

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00177 AC: 2581 AN: 1460762 Hom.: 1 Cov.: 35 AF XY: 0.00167 AC XY: 1212 AN XY: 726674

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00781 AC: 204 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.000134 AC: 7 AN: 52416

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.00196 AC: 2174 AN: 1111968

Other (OTH) AF: 0.00275 AC: 166 AN: 60376

GnomAD4 genome AF: 0.00111 AC: 168 AN: 151820 Hom.: 0 Cov.: 29 AF XY: 0.00102 AC XY: 76 AN XY: 74194

African (AFR) AF: 0.000435 AC: 18 AN: 41418

American (AMR) AF: 0.000982 AC: 15 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 23 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00161 AC: 109 AN: 67898

Other (OTH) AF: 0.00143 AC: 3 AN: 2104

Alfa AF: 0.00182 Hom.: 0

Bravo AF: 0.00120

EpiCase AF: 0.00207

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs538792546; hg19: chr17-1370873;