17-1465784-G-A

Variant names:

• chr17-1465784-G-A
• rs7212008
• NM_001080779.2:c.3166-32C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080779.2(MYO1C):​c.3166-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,315,738 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.016 (63 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (44 hom.)
• Consequence: MYO1C NM_001080779.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.297

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-1465784-G-A is Benign according to our data. Variant chr17-1465784-G-A is described in ClinVar as [Benign]. Clinvar id is 1283328.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1C	NM_001080779.2	c.3166-32C>T		intron_variant	Intron 31 of 31	ENST00000648651.1	NP_001074248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1C	ENST00000648651.1	c.3166-32C>T		intron_variant	Intron 31 of 31		NM_001080779.2	ENSP00000496954.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2460 AN: 152138 Hom.: 63 Cov.: 31

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00528 AC: 629 AN: 119184 AF XY: 0.00385

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.00383

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00142

GnomAD4 exome AF: 0.00154 AC: 1796 AN: 1163482 Hom.: 44 Cov.: 30 AF XY: 0.00131 AC XY: 728 AN XY: 557680

Gnomad4 AFR exome AF: 0.0574 AC: 1432 AN: 24950

Gnomad4 AMR exome AF: 0.00515 AC: 90 AN: 17478

Gnomad4 ASJ exome AF: 0.0000649 AC: 1 AN: 15420

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30526

Gnomad4 SAS exome AF: 0.000140 AC: 4 AN: 28552

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 40088

Gnomad4 NFE exome AF: 0.0000398 AC: 38 AN: 955344

Gnomad4 Remaining exome AF: 0.00465 AC: 216 AN: 46498

GnomAD4 genome AF: 0.0162 AC: 2465 AN: 152256 Hom.: 63 Cov.: 31 AF XY: 0.0159 AC XY: 1180 AN XY: 74436

Gnomad4 AFR AF: 0.0554 AC: 0.0554004 AN: 0.0554004

Gnomad4 AMR AF: 0.00719 AC: 0.00719048 AN: 0.00719048

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000208 AC: 0.000207555 AN: 0.000207555

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000309 AC: 0.000308696 AN: 0.000308696

Gnomad4 OTH AF: 0.0128 AC: 0.012772 AN: 0.012772

Alfa AF: 0.0105 Hom.: 9

Bravo AF: 0.0195

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.75
BranchPoint Hunter		4.0
Mutation Taster		=100/0	polymorphism

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: rs7212008; hg19: chr17-1369078;