17-1465796-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.3166-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,298,706 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (83 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (68 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

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=-0.89).
• BP6: Variant 17-1465796-C-T is Benign according to our data. Variant chr17-1465796-C-T is described in ClinVar as [Benign]. Clinvar id is 1228948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3166-44G>A		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3166-44G>A		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2926 AN: 151982 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00607 AC: 715 AN: 117732 Hom.: 16 AF XY: 0.00440 AC XY: 278 AN XY: 63242

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.00256

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.00371

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00201 AC: 2304 AN: 1146606 Hom.: 68 Cov.: 27 AF XY: 0.00185 AC XY: 1020 AN XY: 549902

Gnomad4 AFR exome AF: 0.0683

Gnomad4 AMR exome AF: 0.00436

Gnomad4 ASJ exome AF: 0.00189

Gnomad4 EAS exome AF: 0.00181

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000230

Gnomad4 OTH exome AF: 0.00492

GnomAD4 genome AF: 0.0192 AC: 2926 AN: 152100 Hom.: 83 Cov.: 32 AF XY: 0.0184 AC XY: 1370 AN XY: 74352

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.00622

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000427

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0103 Hom.: 9

Bravo AF: 0.0227

Asia WGS AF: 0.00375 AC: 13 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

Jul 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.1
Dann	Benign	0.81

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: rs73976221; hg19: chr17-1369090;