NM_001080779.2:c.3165+281A>G

Variant names:

• chr17-1466961-T-C
• rs111340661
• NM_001080779.2:c.3165+281A>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+281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,078 control chromosomes in the GnomAD database, including 729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.087 (729 hom., cov: 32)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.140
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-1466961-T-C is Benign according to our data. Variant chr17-1466961-T-C is described in ClinVar as Benign. ClinVar VariationId is 1284188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 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+281A>G		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3108+281A>G		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.3093+281A>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+281A>G		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3159+281A>G		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3159+281A>G		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13193 AN: 151960 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.0868 AC: 13193 AN: 152078 Hom.: 729 Cov.: 32 AF XY: 0.0926 AC XY: 6879 AN XY: 74324

African (AFR) AF: 0.0274 AC: 1138 AN: 41558

American (AMR) AF: 0.153 AC: 2328 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 336 AN: 3468

East Asian (EAS) AF: 0.114 AC: 591 AN: 5168

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4822

European-Finnish (FIN) AF: 0.184 AC: 1950 AN: 10570

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0923 AC: 6272 AN: 67966

Other (OTH) AF: 0.0904 AC: 191 AN: 2112

Alfa AF: 0.0885 Hom.: 76

Bravo AF: 0.0841

Asia WGS AF: 0.101 AC: 352 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	-0.92
CADD	Benign	4.9
DANN	Benign	0.76
PhyloP100		0.14
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: rs111340661; hg19: chr17-1370255;