17-1467445-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080779.2(MYO1C):c.3065+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,608,666 control chromosomes in the GnomAD database, including 1,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (465 hom., cov: 30)
  • Exomes 𝑓: 0.037 (1339 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0960

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-1467445-C-T is Benign according to our data. Variant chr17-1467445-C-T is described in ClinVar as [Benign]. Clinvar id is 682721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3065+35G>A		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3065+35G>A		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9622 AN: 151862 Hom.: 463 Cov.: 30

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0298

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0403

GnomAD3 exomes AF: 0.0395 AC: 9638 AN: 244164 Hom.: 290 AF XY: 0.0384 AC XY: 5109 AN XY: 133034

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0867

Gnomad EAS exome AF: 0.0000549

Gnomad SAS exome AF: 0.0381

Gnomad FIN exome AF: 0.0187

Gnomad NFE exome AF: 0.0365

Gnomad OTH exome AF: 0.0400

GnomAD4 exome AF: 0.0375 AC: 54556 AN: 1456686 Hom.: 1339 Cov.: 34 AF XY: 0.0378 AC XY: 27389 AN XY: 724882

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0229

Gnomad4 ASJ exome AF: 0.0855

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0397

Gnomad4 FIN exome AF: 0.0207

Gnomad4 NFE exome AF: 0.0353

Gnomad4 OTH exome AF: 0.0424

GnomAD4 genome AF: 0.0634 AC: 9641 AN: 151980 Hom.: 465 Cov.: 30 AF XY: 0.0609 AC XY: 4524 AN XY: 74300

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0927

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.0380

Gnomad4 OTH AF: 0.0399

Alfa AF: 0.0572 Hom.: 77

Bravo AF: 0.0667

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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	-0.81
Cadd	Benign	9.7
Dann	Benign	0.86

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: rs45624734; hg19: chr17-1370739; COSMIC: COSV63001357; COSMIC: COSV63001357;