17-1466961-T-C

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.3165+281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,078 control chromosomes in the GnomAD database, including 729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (729 hom., cov: 32)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.140

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=-0.92).
• BP6: Variant 17-1466961-T-C is Benign according to our data. Variant chr17-1466961-T-C is described in ClinVar as [Benign]. Clinvar id is 1284188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3165+281A>G		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3165+281A>G		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13193 AN: 151960 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0923

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0868 AC: 13193 AN: 152078 Hom.: 729 Cov.: 32 AF XY: 0.0926 AC XY: 6879 AN XY: 74324

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0904

Alfa AF: 0.0885 Hom.: 76

Bravo AF: 0.0841

Asia WGS AF: 0.101 AC: 352 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.9
Dann	Benign	0.76

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: rs111340661; hg19: chr17-1370255;