NM_001080779.2:c.3065+21G>A

Variant names:

• chr17-1467459-C-T
• rs118068886
• NM_001080779.2:c.3065+21G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080779.2(MYO1C):​c.3065+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 1,610,758 control chromosomes in the GnomAD database, including 2,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (170 hom., cov: 29)
  • Exomes 𝑓: 0.052 (2248 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.20

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-1467459-C-T is Benign according to our data. Variant chr17-1467459-C-T is described in ClinVar as [Benign]. Clinvar id is 682784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1C	NM_001080779.2	c.3065+21G>A		intron_variant	Intron 30 of 31	ENST00000648651.1	NP_001074248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1C	ENST00000648651.1	c.3065+21G>A		intron_variant	Intron 30 of 31		NM_001080779.2	ENSP00000496954.1

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5630 AN: 151864 Hom.: 170 Cov.: 29

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0892

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0399

GnomAD3 exomes AF: 0.0379 AC: 9366 AN: 246894 Hom.: 254 AF XY: 0.0372 AC XY: 4997 AN XY: 134274

Gnomad AFR exome AF: 0.0109

Gnomad AMR exome AF: 0.0281

Gnomad ASJ exome AF: 0.0265

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00779

Gnomad FIN exome AF: 0.0316

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0476

GnomAD4 exome AF: 0.0520 AC: 75877 AN: 1458776 Hom.: 2248 Cov.: 35 AF XY: 0.0508 AC XY: 36906 AN XY: 725866

Gnomad4 AFR exome AF: 0.00834

Gnomad4 AMR exome AF: 0.0292

Gnomad4 ASJ exome AF: 0.0252

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00865

Gnomad4 FIN exome AF: 0.0311

Gnomad4 NFE exome AF: 0.0617

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0370 AC: 5628 AN: 151982 Hom.: 170 Cov.: 29 AF XY: 0.0346 AC XY: 2567 AN XY: 74290

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00893

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0390

Alfa AF: 0.0253 Hom.: 13

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs118068886; hg19: chr17-1370753;