rs2302458

Variant names:

• chr17-1467248-C-A
• rs2302458
• NM_001080779.2:c.3159G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001080779.2(MYO1C):​c.3159G>T​(p.Leu1053Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,611,446 control chromosomes in the GnomAD database, including 8,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (747 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7313 hom.)
• Consequence: MYO1C NM_001080779.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.653
• Publications: 16 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 17-1467248-C-A is Benign according to our data. Variant chr17-1467248-C-A is described in ClinVar as Benign. ClinVar VariationId is 508122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.653 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.3159G>T	p.Leu1053Leu	synonymous	Exon 31 of 32	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3102G>T	p.Leu1034Leu	synonymous	Exon 31 of 32	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.3087G>T	p.Leu1029Leu	synonymous	Exon 31 of 32	NP_001350784.1	F5H6E2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1C	ENST00000648651.1	MANE Select	c.3159G>T	p.Leu1053Leu	synonymous	Exon 31 of 32	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3153G>T	p.Leu1051Leu	synonymous	Exon 31 of 32	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3153G>T	p.Leu1051Leu	synonymous	Exon 31 of 32	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14811 AN: 152142 Hom.: 742 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0967

GnomAD2 exomes AF: 0.0808 AC: 19771 AN: 244766 AF XY: 0.0809

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0520

Gnomad ASJ exome AF: 0.0571

Gnomad EAS exome AF: 0.0874

Gnomad FIN exome AF: 0.0469

Gnomad NFE exome AF: 0.0966

Gnomad OTH exome AF: 0.0858

GnomAD4 exome AF: 0.0967 AC: 141157 AN: 1459186 Hom.: 7313 Cov.: 34 AF XY: 0.0956 AC XY: 69371 AN XY: 725670

African (AFR) AF: 0.115 AC: 3849 AN: 33444

American (AMR) AF: 0.0546 AC: 2428 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.0604 AC: 1575 AN: 26068

East Asian (EAS) AF: 0.132 AC: 5247 AN: 39660

South Asian (SAS) AF: 0.0647 AC: 5547 AN: 85738

European-Finnish (FIN) AF: 0.0494 AC: 2621 AN: 53102

Middle Eastern (MID) AF: 0.0566 AC: 326 AN: 5760

European-Non Finnish (NFE) AF: 0.103 AC: 114169 AN: 1110678

Other (OTH) AF: 0.0895 AC: 5395 AN: 60284

GnomAD4 genome AF: 0.0975 AC: 14839 AN: 152260 Hom.: 747 Cov.: 32 AF XY: 0.0939 AC XY: 6994 AN XY: 74446

African (AFR) AF: 0.117 AC: 4875 AN: 41546

American (AMR) AF: 0.0789 AC: 1207 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3472

East Asian (EAS) AF: 0.101 AC: 524 AN: 5184

South Asian (SAS) AF: 0.0694 AC: 335 AN: 4826

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10626

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

European-Non Finnish (NFE) AF: 0.101 AC: 6865 AN: 67986

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0979 Hom.: 1104

Bravo AF: 0.0998

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.65
Mutation Taster		=85/15	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2302458; hg19: chr17-1370542; COSMIC: COSV62998816; COSMIC: COSV62998816;