17-1467629-C-A

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.2968-52G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,545,948 control chromosomes in the GnomAD database, including 930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (384 hom., cov: 27)
  • Exomes 𝑓: 0.0055 (546 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.206

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=-0.82).
• BP6: Variant 17-1467629-C-A is Benign according to our data. Variant chr17-1467629-C-A is described in ClinVar as [Benign]. Clinvar id is 1273128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.2968-52G>T		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.2968-52G>T		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5438 AN: 140394 Hom.: 385 Cov.: 27

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00414

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000460

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0372

GnomAD3 exomes AF: 0.0132 AC: 3118 AN: 235608 Hom.: 197 AF XY: 0.00989 AC XY: 1272 AN XY: 128600

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.00901

Gnomad ASJ exome AF: 0.00411

Gnomad EAS exome AF: 0.0000559

Gnomad SAS exome AF: 0.000566

Gnomad FIN exome AF: 0.0000635

Gnomad NFE exome AF: 0.000690

Gnomad OTH exome AF: 0.00783

GnomAD4 exome AF: 0.00552 AC: 7759 AN: 1405452 Hom.: 546 Cov.: 27 AF XY: 0.00486 AC XY: 3407 AN XY: 701438

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.0000452

Gnomad4 NFE exome AF: 0.000558

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0387 AC: 5433 AN: 140496 Hom.: 384 Cov.: 27 AF XY: 0.0365 AC XY: 2497 AN XY: 68322

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.00414

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000230

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000721

Gnomad4 OTH AF: 0.0368

Alfa AF: 0.00828 Hom.: 11

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

Jul 01, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.6
Dann	Benign	0.54

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: rs115083063; hg19: chr17-1370923;