17-1467426-C-T

Variant names:

• chr17-1467426-C-T
• rs2302457
• NM_001080779.2:c.3065+54G>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+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,598,196 control chromosomes in the GnomAD database, including 130,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9898 hom., cov: 28)
  • Exomes 𝑓: 0.41 (120256 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.551
• Publications: 7 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=-0.85).
• BP6: Variant 17-1467426-C-T is Benign according to our data. Variant chr17-1467426-C-T is described in ClinVar as Benign. ClinVar VariationId is 1254983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 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+54G>A		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3008+54G>A		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.2993+54G>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+54G>A		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3059+54G>A		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3059+54G>A		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53526 AN: 151020 Hom.: 9899 Cov.: 28

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.405 AC: 586096 AN: 1447060 Hom.: 120256 Cov.: 33 AF XY: 0.406 AC XY: 292455 AN XY: 720094

African (AFR) AF: 0.241 AC: 8025 AN: 33274

American (AMR) AF: 0.364 AC: 16001 AN: 44010

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9034 AN: 25976

East Asian (EAS) AF: 0.356 AC: 14039 AN: 39396

South Asian (SAS) AF: 0.422 AC: 36172 AN: 85758

European-Finnish (FIN) AF: 0.317 AC: 15449 AN: 48756

Middle Eastern (MID) AF: 0.348 AC: 1988 AN: 5716

European-Non Finnish (NFE) AF: 0.419 AC: 462451 AN: 1104260

Other (OTH) AF: 0.383 AC: 22937 AN: 59914

GnomAD4 genome AF: 0.354 AC: 53558 AN: 151136 Hom.: 9898 Cov.: 28 AF XY: 0.352 AC XY: 25936 AN XY: 73784

African (AFR) AF: 0.247 AC: 10176 AN: 41238

American (AMR) AF: 0.392 AC: 5961 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1205 AN: 3464

East Asian (EAS) AF: 0.332 AC: 1677 AN: 5048

South Asian (SAS) AF: 0.415 AC: 1984 AN: 4786

European-Finnish (FIN) AF: 0.312 AC: 3282 AN: 10510

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.416 AC: 28125 AN: 67606

Other (OTH) AF: 0.383 AC: 802 AN: 2094

Alfa AF: 0.377 Hom.: 1373

Bravo AF: 0.353

Asia WGS AF: 0.369 AC: 1282 AN: 3476

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	-0.85
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		-0.55
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: rs2302457; hg19: chr17-1370720; COSMIC: COSV63000074; COSMIC: COSV63000074;