17-1467165-T-C

Variant names:

• chr17-1467165-T-C
• rs2302459
• NM_001080779.2:c.3165+77A>G

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.3165+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,388,400 control chromosomes in the GnomAD database, including 374,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45561 hom., cov: 32)
  • Exomes 𝑓: 0.73 (329423 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33
• Publications: 12 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=-0.75).
• BP6: Variant 17-1467165-T-C is Benign according to our data. Variant chr17-1467165-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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.3165+77A>G		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3108+77A>G		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.3093+77A>G		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.3165+77A>G		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3159+77A>G		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3159+77A>G		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116944 AN: 151992 Hom.: 45514 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.729 AC: 901135 AN: 1236290 Hom.: 329423 AF XY: 0.727 AC XY: 449717 AN XY: 618234

African (AFR) AF: 0.887 AC: 25384 AN: 28626

American (AMR) AF: 0.711 AC: 25474 AN: 35838

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 18046 AN: 24226

East Asian (EAS) AF: 0.638 AC: 22553 AN: 35352

South Asian (SAS) AF: 0.707 AC: 53898 AN: 76200

European-Finnish (FIN) AF: 0.708 AC: 29141 AN: 41150

Middle Eastern (MID) AF: 0.632 AC: 3185 AN: 5040

European-Non Finnish (NFE) AF: 0.731 AC: 685116 AN: 936968

Other (OTH) AF: 0.725 AC: 38338 AN: 52890

GnomAD4 genome AF: 0.770 AC: 117049 AN: 152110 Hom.: 45561 Cov.: 32 AF XY: 0.766 AC XY: 56932 AN XY: 74346

African (AFR) AF: 0.889 AC: 36911 AN: 41506

American (AMR) AF: 0.765 AC: 11689 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2574 AN: 3468

East Asian (EAS) AF: 0.572 AC: 2950 AN: 5158

South Asian (SAS) AF: 0.709 AC: 3415 AN: 4820

European-Finnish (FIN) AF: 0.701 AC: 7426 AN: 10588

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49618 AN: 67972

Other (OTH) AF: 0.768 AC: 1623 AN: 2112

Alfa AF: 0.739 Hom.: 46240

Bravo AF: 0.775

Asia WGS AF: 0.678 AC: 2360 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	-0.75
CADD	Benign	4.1
DANN	Benign	0.78
PhyloP100		-1.3
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: rs2302459; hg19: chr17-1370459; COSMIC: COSV62999101; COSMIC: COSV62999101;