rs11538162

Variant names:

• chr17-1465529-G-A
• rs11538162
• NM_001080779.2:c.*197C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001080779.2(MYO1C):​c.*197C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 497,876 control chromosomes in the GnomAD database, including 1,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (298 hom., cov: 32)
  • Exomes 𝑓: 0.062 (770 hom.)
• Consequence: MYO1C NM_001080779.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.48
• Publications: 2 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 17-1465529-G-A is Benign according to our data. Variant chr17-1465529-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 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.*197C>T		3_prime_UTR	Exon 32 of 32	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.*197C>T		3_prime_UTR	Exon 32 of 32	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.*197C>T		3_prime_UTR	Exon 32 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.*197C>T		3_prime_UTR	Exon 32 of 32	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.*197C>T		3_prime_UTR	Exon 32 of 32	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.*197C>T		3_prime_UTR	Exon 32 of 32	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8123 AN: 152132 Hom.: 299 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0618

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0623 AC: 21532 AN: 345626 Hom.: 770 Cov.: 5 AF XY: 0.0634 AC XY: 11060 AN XY: 174546

African (AFR) AF: 0.0192 AC: 177 AN: 9222

American (AMR) AF: 0.0390 AC: 320 AN: 8214

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 1256 AN: 9758

East Asian (EAS) AF: 0.000788 AC: 19 AN: 24116

South Asian (SAS) AF: 0.118 AC: 682 AN: 5772

European-Finnish (FIN) AF: 0.0640 AC: 1843 AN: 28806

Middle Eastern (MID) AF: 0.0890 AC: 239 AN: 2686

European-Non Finnish (NFE) AF: 0.0660 AC: 15660 AN: 237382

Other (OTH) AF: 0.0679 AC: 1336 AN: 19670

GnomAD4 genome AF: 0.0533 AC: 8120 AN: 152250 Hom.: 298 Cov.: 32 AF XY: 0.0546 AC XY: 4065 AN XY: 74446

African (AFR) AF: 0.0198 AC: 823 AN: 41570

American (AMR) AF: 0.0545 AC: 834 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5180

South Asian (SAS) AF: 0.122 AC: 586 AN: 4816

European-Finnish (FIN) AF: 0.0618 AC: 656 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0663 AC: 4507 AN: 67998

Other (OTH) AF: 0.0559 AC: 118 AN: 2112

Alfa AF: 0.0570 Hom.: 132

Bravo AF: 0.0492

Asia WGS AF: 0.0590 AC: 205 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	-0.22
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		1.5
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: rs11538162; hg19: chr17-1368823;