17-1467629-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080779.2(MYO1C):​c.2968-52G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,545,948 control chromosomes in the GnomAD database, including 930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (384 hom., cov: 27)
  • Exomes 𝑓: 0.0055 (546 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-1467629-C-A is Benign according to our data. Variant chr17-1467629-C-A is described in ClinVar as Benign. ClinVar VariationId is 1273128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

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>T		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.2911-52G>T		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.2896-52G>T		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>T		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.2962-52G>T		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.2962-52G>T		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5438 AN: 140394 Hom.: 385 Cov.: 27

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00414

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000460

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0372

GnomAD2 exomes AF: 0.0132 AC: 3118 AN: 235608 AF XY: 0.00989

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.00901

Gnomad ASJ exome AF: 0.00411

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.0000635

Gnomad NFE exome AF: 0.000690

Gnomad OTH exome AF: 0.00783

GnomAD4 exome AF: 0.00552 AC: 7759 AN: 1405452 Hom.: 546 Cov.: 27 AF XY: 0.00486 AC XY: 3407 AN XY: 701438

African (AFR) AF: 0.176 AC: 5719 AN: 32430

American (AMR) AF: 0.0108 AC: 475 AN: 44106

Ashkenazi Jewish (ASJ) AF: 0.00392 AC: 101 AN: 25752

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39258

South Asian (SAS) AF: 0.000661 AC: 56 AN: 84734

European-Finnish (FIN) AF: 0.0000452 AC: 2 AN: 44254

Middle Eastern (MID) AF: 0.0102 AC: 48 AN: 4708

European-Non Finnish (NFE) AF: 0.000558 AC: 598 AN: 1071616

Other (OTH) AF: 0.0129 AC: 758 AN: 58594

GnomAD4 genome AF: 0.0387 AC: 5433 AN: 140496 Hom.: 384 Cov.: 27 AF XY: 0.0365 AC XY: 2497 AN XY: 68322

African (AFR) AF: 0.142 AC: 5062 AN: 35626

American (AMR) AF: 0.0168 AC: 238 AN: 14176

Ashkenazi Jewish (ASJ) AF: 0.00414 AC: 14 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4764

South Asian (SAS) AF: 0.000230 AC: 1 AN: 4344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000721 AC: 47 AN: 65182

Other (OTH) AF: 0.0368 AC: 71 AN: 1928

Alfa AF: 0.0121 Hom.: 16

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs115083063; hg19: chr17-1370923;