17-1467579-T-TG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001080779.2(MYO1C):c.2968-3_2968-2insC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,612,582 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (1 hom.)
• Consequence: MYO1C NM_001080779.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.50

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-1467579-T-TG is Benign according to our data. Variant chr17-1467579-T-TG is described in ClinVar as [Benign]. Clinvar id is 1291838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.2968-3_2968-2insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.2968-3_2968-2insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 151702 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00110 AC: 275 AN: 249610 Hom.: 0 AF XY: 0.00125 AC XY: 169 AN XY: 135276

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00867

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000960

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00177 AC: 2581 AN: 1460762 Hom.: 1 Cov.: 35 AF XY: 0.00167 AC XY: 1212 AN XY: 726674

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000134

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.00111 AC: 168 AN: 151820 Hom.: 0 Cov.: 29 AF XY: 0.00102 AC XY: 76 AN XY: 74194

Gnomad4 AFR AF: 0.000435

Gnomad4 AMR AF: 0.000982

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00161

Gnomad4 OTH AF: 0.00143

Bravo AF: 0.00120

EpiCase AF: 0.00207

EpiControl AF: 0.00190

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

Dec 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs538792546; hg19: chr17-1370873;