15-59137366-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004998.4(MYO1E):c.*14C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,613,270 control chromosomes in the GnomAD database, including 496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (169 hom., cov: 32)
  • Exomes 𝑓: 0.011 (327 hom.)
• Consequence: MYO1E NM_004998.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.188

Genes affected

MYO1E (HGNC:7599): (myosin IE) This gene encodes a member of the nonmuscle class I myosins which are a subgroup of the unconventional myosin protein family. The unconventional myosin proteins function as actin-based molecular motors. Class I myosins are characterized by a head (motor) domain, a regulatory domain and a either a short or long tail domain. Among the class I myosins, this protein is distinguished by a long tail domain that is involved in crosslinking actin filaments. This protein localizes to the cytoplasm and may be involved in intracellular movement and membrane trafficking. Mutations in this gene are the cause of focal segmental glomerulosclerosis-6. This gene has been referred to as myosin IC in the literature but is distinct from the myosin IC gene located on chromosome 17. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-59137366-G-C is Benign according to our data. Variant chr15-59137366-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1294548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-59137366-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1E	NM_004998.4	c.*14C>G		3_prime_UTR_variant	28/28	ENST00000288235.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1E	ENST00000288235.9	c.*14C>G		3_prime_UTR_variant	28/28	1	NM_004998.4	P1
MYO1E	ENST00000559412.1	c.130-589C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5203 AN: 152160 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00635

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0215 AC: 5396 AN: 251350 Hom.: 123 AF XY: 0.0194 AC XY: 2642 AN XY: 135848

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.0308

Gnomad SAS exome AF: 0.0133

Gnomad FIN exome AF: 0.0518

Gnomad NFE exome AF: 0.00753

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0114 AC: 16646 AN: 1460992 Hom.: 327 Cov.: 30 AF XY: 0.0111 AC XY: 8040 AN XY: 726878

Gnomad4 AFR exome AF: 0.0873

Gnomad4 AMR exome AF: 0.0196

Gnomad4 ASJ exome AF: 0.0357

Gnomad4 EAS exome AF: 0.0457

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.0526

Gnomad4 NFE exome AF: 0.00454

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0343 AC: 5216 AN: 152278 Hom.: 169 Cov.: 32 AF XY: 0.0361 AC XY: 2686 AN XY: 74446

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0377

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0221 Hom.: 18

Bravo AF: 0.0335

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Kidney disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 06, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 15, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.8
Dann	Benign	0.53

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: rs3751538; hg19: chr15-59429565;