15-59137272-T-G

Position:

• chr15-59137272-T-G

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.*108A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 1,027,896 control chromosomes in the GnomAD database, including 591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (266 hom., cov: 32)
  • Exomes 𝑓: 0.021 (325 hom.)
• Consequence: MYO1E NM_004998.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.112

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=-0.79).
• BP6: Variant 15-59137272-T-G is Benign according to our data. Variant chr15-59137272-T-G is described in ClinVar as [Benign]. Clinvar id is 1267843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1E	NM_004998.4	c.*108A>C		3_prime_UTR_variant	28/28	ENST00000288235.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1E	ENST00000288235.9	c.*108A>C		3_prime_UTR_variant	28/28	1	NM_004998.4	P1
MYO1E	ENST00000559412.1	c.130-495A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6580 AN: 152070 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0210 AC: 18432 AN: 875708 Hom.: 325 Cov.: 12 AF XY: 0.0200 AC XY: 9142 AN XY: 456094

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.00777

Gnomad4 SAS exome AF: 0.00627

Gnomad4 FIN exome AF: 0.00659

Gnomad4 NFE exome AF: 0.0211

Gnomad4 OTH exome AF: 0.0280

GnomAD4 genome AF: 0.0434 AC: 6606 AN: 152188 Hom.: 266 Cov.: 32 AF XY: 0.0422 AC XY: 3139 AN XY: 74420

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0298

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0282 Hom.: 34

Bravo AF: 0.0487

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8041633; hg19: chr15-59429471;