17-1467165-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+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,388,400 control chromosomes in the GnomAD database, including 374,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45561 hom., cov: 32)
  • Exomes 𝑓: 0.73 (329423 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

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=-0.75).
• BP6: Variant 17-1467165-T-C is Benign according to our data. Variant chr17-1467165-T-C is described in ClinVar as [Benign]. Clinvar id is 1266641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3165+77A>G		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3165+77A>G		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116944 AN: 151992 Hom.: 45514 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.729 AC: 901135 AN: 1236290 Hom.: 329423 AF XY: 0.727 AC XY: 449717 AN XY: 618234

Gnomad4 AFR exome AF: 0.887

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.638

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.725

GnomAD4 genome AF: 0.770 AC: 117049 AN: 152110 Hom.: 45561 Cov.: 32 AF XY: 0.766 AC XY: 56932 AN XY: 74346

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.768

Alfa AF: 0.730 Hom.: 33072

Bravo AF: 0.775

Asia WGS AF: 0.678 AC: 2360 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 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	4.1
Dann	Benign	0.78

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: rs2302459; hg19: chr17-1370459; COSMIC: COSV62999101; COSMIC: COSV62999101;