17-1467449-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001080779.2(MYO1C):c.3065+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,577,112 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (5 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (37 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.831

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=-0.85).
• BP6: Variant 17-1467449-G-A is Benign according to our data. Variant chr17-1467449-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00279 (370/132714) while in subpopulation EAS AF= 0.0195 (88/4512). AF 95% confidence interval is 0.0162. There are 5 homozygotes in gnomad4. There are 191 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 366 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.3065+31C>T		intron_variant		ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.3065+31C>T		intron_variant			NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 366 AN: 132618 Hom.: 5 Cov.: 29

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000168

Gnomad OTH AF: 0.00395

GnomAD3 exomes AF: 0.00488 AC: 1195 AN: 244934 Hom.: 16 AF XY: 0.00373 AC XY: 498 AN XY: 133428

Gnomad AFR exome AF: 0.000640

Gnomad AMR exome AF: 0.0244

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0173

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000902

Gnomad OTH exome AF: 0.00351

GnomAD4 exome AF: 0.00175 AC: 2529 AN: 1444398 Hom.: 37 Cov.: 34 AF XY: 0.00163 AC XY: 1169 AN XY: 718944

Gnomad4 AFR exome AF: 0.000633

Gnomad4 AMR exome AF: 0.0273

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0286

Gnomad4 SAS exome AF: 0.0000931

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000962

Gnomad4 OTH exome AF: 0.00125

GnomAD4 genome AF: 0.00279 AC: 370 AN: 132714 Hom.: 5 Cov.: 29 AF XY: 0.00294 AC XY: 191 AN XY: 64860

Gnomad4 AFR AF: 0.00133

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000168

Gnomad4 OTH AF: 0.00391

Alfa AF: 0.000236 Hom.: 0

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.85
Cadd	Benign	0.17
Dann	Benign	0.89

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: rs45484695; hg19: chr17-1370743; COSMIC: COSV62999162; COSMIC: COSV62999162;