15-59137959-G-A

Position:

• chr15-59137959-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004998.4(MYO1E):​c.3250+239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,216 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.066 (333 hom., cov: 32)
• Consequence: MYO1E NM_004998.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-59137959-G-A is Benign according to our data. Variant chr15-59137959-G-A is described in ClinVar as [Benign]. Clinvar id is 1237680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1E	NM_004998.4	c.3250+239C>T		intron_variant		ENST00000288235.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1E	ENST00000288235.9	c.3250+239C>T		intron_variant		1	NM_004998.4	P1
MYO1E	ENST00000559412.1	c.129+333C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9962 AN: 152098 Hom.: 332 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0560

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0655 AC: 9972 AN: 152216 Hom.: 333 Cov.: 32 AF XY: 0.0660 AC XY: 4911 AN XY: 74416

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.0768

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0192

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0397 Hom.: 28

Bravo AF: 0.0674

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.52

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: rs76569455; hg19: chr15-59430158;