17-1465839-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.3166-87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,050,734 control chromosomes in the GnomAD database, including 5,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.096 (714 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4740 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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=-1.02).
• BP6: Variant 17-1465839-T-C is Benign according to our data. Variant chr17-1465839-T-C is described in ClinVar as [Benign]. Clinvar id is 683250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3166-87A>G		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3166-87A>G		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14531 AN: 152056 Hom.: 709 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0980

GnomAD4 exome AF: 0.0996 AC: 89487 AN: 898560 Hom.: 4740 AF XY: 0.0991 AC XY: 43368 AN XY: 437688

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0553

Gnomad4 ASJ exome AF: 0.0628

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0701

Gnomad4 FIN exome AF: 0.0492

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0900

GnomAD4 genome AF: 0.0957 AC: 14560 AN: 152174 Hom.: 714 Cov.: 32 AF XY: 0.0923 AC XY: 6867 AN XY: 74396

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.0987 Hom.: 124

Bravo AF: 0.0979

Asia WGS AF: 0.0940 AC: 325 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

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.65
Dann	Benign	0.14

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: rs76446640; hg19: chr17-1369133;