rs74477362

Variant names:

• chr17-1465617-C-T
• rs74477362
• NM_001080779.2:c.*109G>A

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.*109G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,161,488 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (58 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (36 hom.)
• Consequence: MYO1C NM_001080779.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.22
• 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=-0.91).
• BP6: Variant 17-1465617-C-T is Benign according to our data. Variant chr17-1465617-C-T is described in ClinVar as Benign. ClinVar VariationId is 1276129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 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.*109G>A		3_prime_UTR	Exon 32 of 32	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.*109G>A		3_prime_UTR	Exon 32 of 32	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.*109G>A		3_prime_UTR	Exon 32 of 32	NP_001350784.1	F5H6E2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1C	ENST00000648651.1	MANE Select	c.*109G>A		3_prime_UTR	Exon 32 of 32	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.*109G>A		3_prime_UTR	Exon 32 of 32	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.*109G>A		3_prime_UTR	Exon 32 of 32	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2434 AN: 151854 Hom.: 58 Cov.: 31

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00912

GnomAD4 exome AF: 0.00157 AC: 1582 AN: 1009516 Hom.: 36 Cov.: 14 AF XY: 0.00139 AC XY: 683 AN XY: 490350

African (AFR) AF: 0.0598 AC: 1285 AN: 21488

American (AMR) AF: 0.00244 AC: 42 AN: 17220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14544

East Asian (EAS) AF: 0.000707 AC: 21 AN: 29694

South Asian (SAS) AF: 0.000212 AC: 6 AN: 28304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40832

Middle Eastern (MID) AF: 0.00253 AC: 11 AN: 4354

European-Non Finnish (NFE) AF: 0.0000788 AC: 64 AN: 811702

Other (OTH) AF: 0.00370 AC: 153 AN: 41378

GnomAD4 genome AF: 0.0160 AC: 2435 AN: 151972 Hom.: 58 Cov.: 31 AF XY: 0.0156 AC XY: 1156 AN XY: 74290

African (AFR) AF: 0.0557 AC: 2308 AN: 41428

American (AMR) AF: 0.00485 AC: 74 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00214 AC: 11 AN: 5146

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67968

Other (OTH) AF: 0.00902 AC: 19 AN: 2106

Alfa AF: 0.00715 Hom.: 11

Bravo AF: 0.0173

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.91
CADD	Benign	0.092
DANN	Benign	0.54
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism

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: rs74477362; hg19: chr17-1368911;