17-1467794-T-C

Position:

• chr17-1467794-T-C

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.2967+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (27057 hom., cov: 11)
  • Exomes 𝑓: 0.73 (135896 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.117

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=-0.92).
• BP6: Variant 17-1467794-T-C is Benign according to our data. Variant chr17-1467794-T-C is described in ClinVar as [Benign]. Clinvar id is 1240817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1C	NM_001080779.2	c.2967+46A>G		intron_variant		ENST00000648651.1	NP_001074248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1C	ENST00000648651.1	c.2967+46A>G		intron_variant			NM_001080779.2	ENSP00000496954

Frequencies

GnomAD3 genomes AF: 0.756 AC: 70038 AN: 92644 Hom.: 27026 Cov.: 11

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.569

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.759

GnomAD3 exomes AF: 0.747 AC: 102918 AN: 137776 Hom.: 37096 AF XY: 0.744 AC XY: 54959 AN XY: 73898

Gnomad AFR exome AF: 0.898

Gnomad AMR exome AF: 0.756

Gnomad ASJ exome AF: 0.759

Gnomad EAS exome AF: 0.644

Gnomad SAS exome AF: 0.746

Gnomad FIN exome AF: 0.686

Gnomad NFE exome AF: 0.755

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.729 AC: 381880 AN: 523918 Hom.: 135896 Cov.: 6 AF XY: 0.727 AC XY: 203586 AN XY: 280016

Gnomad4 AFR exome AF: 0.888

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.733

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.756 AC: 70103 AN: 92716 Hom.: 27057 Cov.: 11 AF XY: 0.752 AC XY: 32346 AN XY: 43004

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.756

Alfa AF: 0.745 Hom.: 7688

Bravo AF: 0.776

Asia WGS AF: 0.634 AC: 2032 AN: 3202

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.12

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: rs8069059; hg19: chr17-1371088;