17-1467248-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001080779.2(MYO1C):c.3159G>T(p.Leu1053=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,611,446 control chromosomes in the GnomAD database, including 8,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (747 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7313 hom.)
• Consequence: MYO1C NM_001080779.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.653

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 17-1467248-C-A is Benign according to our data. Variant chr17-1467248-C-A is described in ClinVar as [Benign]. Clinvar id is 508122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.653 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3159G>T	p.Leu1053=	synonymous_variant	31/32	ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3159G>T	p.Leu1053=	synonymous_variant	31/32		NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14811 AN: 152142 Hom.: 742 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0967

GnomAD3 exomes AF: 0.0808 AC: 19771 AN: 244766 Hom.: 837 AF XY: 0.0809 AC XY: 10746 AN XY: 132758

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0520

Gnomad ASJ exome AF: 0.0571

Gnomad EAS exome AF: 0.0874

Gnomad SAS exome AF: 0.0643

Gnomad FIN exome AF: 0.0469

Gnomad NFE exome AF: 0.0966

Gnomad OTH exome AF: 0.0858

GnomAD4 exome AF: 0.0967 AC: 141157 AN: 1459186 Hom.: 7313 Cov.: 34 AF XY: 0.0956 AC XY: 69371 AN XY: 725670

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0546

Gnomad4 ASJ exome AF: 0.0604

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0647

Gnomad4 FIN exome AF: 0.0494

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0895

GnomAD4 genome AF: 0.0975 AC: 14839 AN: 152260 Hom.: 747 Cov.: 32 AF XY: 0.0939 AC XY: 6994 AN XY: 74446

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0974 Hom.: 877

Bravo AF: 0.0998

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

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	-0.26
Cadd	Benign	11
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2302458; hg19: chr17-1370542; COSMIC: COSV62998816; COSMIC: COSV62998816;