rs45624734

Variant names:

• chr17-1467445-C-T
• rs45624734
• NM_001080779.2:c.3065+35G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-1467445-C-T
• chr17-1467445-C-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.3065+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,608,666 control chromosomes in the GnomAD database, including 1,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (465 hom., cov: 30)
  • Exomes 𝑓: 0.037 (1339 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960
• Publications: 5 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=-0.81).
• BP6: Variant 17-1467445-C-T is Benign according to our data. Variant chr17-1467445-C-T is described in ClinVar as Benign. ClinVar VariationId is 682721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 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.3065+35G>A		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3008+35G>A		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.2993+35G>A		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.3065+35G>A		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3059+35G>A		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3059+35G>A		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9622 AN: 151862 Hom.: 463 Cov.: 30

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0298

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0403

GnomAD2 exomes AF: 0.0395 AC: 9638 AN: 244164 AF XY: 0.0384

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0867

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.0187

Gnomad NFE exome AF: 0.0365

Gnomad OTH exome AF: 0.0400

GnomAD4 exome AF: 0.0375 AC: 54556 AN: 1456686 Hom.: 1339 Cov.: 34 AF XY: 0.0378 AC XY: 27389 AN XY: 724882

African (AFR) AF: 0.141 AC: 4725 AN: 33438

American (AMR) AF: 0.0229 AC: 1022 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 2230 AN: 26068

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39654

South Asian (SAS) AF: 0.0397 AC: 3416 AN: 86136

European-Finnish (FIN) AF: 0.0207 AC: 1046 AN: 50494

Middle Eastern (MID) AF: 0.0547 AC: 315 AN: 5756

European-Non Finnish (NFE) AF: 0.0353 AC: 39243 AN: 1110276

Other (OTH) AF: 0.0424 AC: 2558 AN: 60276

GnomAD4 genome AF: 0.0634 AC: 9641 AN: 151980 Hom.: 465 Cov.: 30 AF XY: 0.0609 AC XY: 4524 AN XY: 74300

African (AFR) AF: 0.138 AC: 5721 AN: 41438

American (AMR) AF: 0.0322 AC: 492 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 322 AN: 3472

East Asian (EAS) AF: 0.000776 AC: 4 AN: 5152

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4822

European-Finnish (FIN) AF: 0.0220 AC: 233 AN: 10592

Middle Eastern (MID) AF: 0.0414 AC: 12 AN: 290

European-Non Finnish (NFE) AF: 0.0380 AC: 2579 AN: 67930

Other (OTH) AF: 0.0399 AC: 84 AN: 2104

Alfa AF: 0.0572 Hom.: 77

Bravo AF: 0.0667

Asia WGS AF: 0.0220 AC: 77 AN: 3478

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	-0.81
CADD	Benign	9.7
DANN	Benign	0.86
PhyloP100		-0.096
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: rs45624734; hg19: chr17-1370739; COSMIC: COSV63001357; COSMIC: COSV63001357;