17-1467449-G-A

Variant names:

• chr17-1467449-G-A
• rs45484695
• NM_001080779.2:c.3065+31C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001080779.2(MYO1C):​c.3065+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,577,112 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (5 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (37 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.831
• 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=-0.85).
• BP6: Variant 17-1467449-G-A is Benign according to our data. Variant chr17-1467449-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1316116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00279 (370/132714) while in subpopulation EAS AF = 0.0195 (88/4512). AF 95% confidence interval is 0.0162. There are 5 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 370 AD gene.

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+31C>T		intron	N/A	NP_001074248.1	O00159-1
	MYO1C	NM_001080950.2		c.3008+31C>T		intron	N/A	NP_001074419.1	O00159-3
	MYO1C	NM_001363855.1		c.2993+31C>T		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+31C>T		intron	N/A	ENSP00000496954.1	O00159-1
	MYO1C	ENST00000934819.1		c.3059+31C>T		intron	N/A	ENSP00000604878.1
	MYO1C	ENST00000969312.1		c.3059+31C>T		intron	N/A	ENSP00000639371.1

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 366 AN: 132618 Hom.: 5 Cov.: 29

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000168

Gnomad OTH AF: 0.00395

GnomAD2 exomes AF: 0.00488 AC: 1195 AN: 244934 AF XY: 0.00373

Gnomad AFR exome AF: 0.000640

Gnomad AMR exome AF: 0.0244

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000902

Gnomad OTH exome AF: 0.00351

GnomAD4 exome AF: 0.00175 AC: 2529 AN: 1444398 Hom.: 37 Cov.: 34 AF XY: 0.00163 AC XY: 1169 AN XY: 718944

African (AFR) AF: 0.000633 AC: 21 AN: 33150

American (AMR) AF: 0.0273 AC: 1208 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25632

East Asian (EAS) AF: 0.0286 AC: 1109 AN: 38794

South Asian (SAS) AF: 0.0000931 AC: 8 AN: 85974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49282

Middle Eastern (MID) AF: 0.000528 AC: 3 AN: 5682

European-Non Finnish (NFE) AF: 0.0000962 AC: 106 AN: 1102226

Other (OTH) AF: 0.00125 AC: 74 AN: 59366

GnomAD4 genome AF: 0.00279 AC: 370 AN: 132714 Hom.: 5 Cov.: 29 AF XY: 0.00294 AC XY: 191 AN XY: 64860

African (AFR) AF: 0.00133 AC: 49 AN: 36834

American (AMR) AF: 0.0167 AC: 216 AN: 12966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3208

East Asian (EAS) AF: 0.0195 AC: 88 AN: 4512

South Asian (SAS) AF: 0.00 AC: 0 AN: 3966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.000168 AC: 10 AN: 59394

Other (OTH) AF: 0.00391 AC: 7 AN: 1790

Alfa AF: 0.000236 Hom.: 0

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	0.17
DANN	Benign	0.89
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism

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: rs45484695; hg19: chr17-1370743; COSMIC: COSV62999162; COSMIC: COSV62999162;