17-1466044-T-C

Variant names:

• chr17-1466044-T-C
• rs112614619
• NM_001080779.2:c.3166-292A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080779.2(MYO1C):​c.3166-292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,024 control chromosomes in the GnomAD database, including 717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.096 (717 hom., cov: 31)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.893
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 17-1466044-T-C is Benign according to our data. Variant chr17-1466044-T-C is described in ClinVar as Benign. ClinVar VariationId is 1249204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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.3166-292A>G		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3109-292A>G		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.3094-292A>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.3166-292A>G		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3160-292A>G		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3160-292A>G		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14524 AN: 151906 Hom.: 712 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0997

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0986

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0957 AC: 14553 AN: 152024 Hom.: 717 Cov.: 31 AF XY: 0.0923 AC XY: 6856 AN XY: 74314

African (AFR) AF: 0.112 AC: 4643 AN: 41470

American (AMR) AF: 0.0784 AC: 1197 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3468

East Asian (EAS) AF: 0.100 AC: 516 AN: 5162

South Asian (SAS) AF: 0.0702 AC: 338 AN: 4812

European-Finnish (FIN) AF: 0.0418 AC: 442 AN: 10576

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6823 AN: 67954

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0839 Hom.: 190

Bravo AF: 0.0979

Asia WGS AF: 0.0940 AC: 326 AN: 3478

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
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.41
PhyloP100		-0.89
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: rs112614619; hg19: chr17-1369338;