15-59137741-G-C

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.3251-285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,106 control chromosomes in the GnomAD database, including 7,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7005 hom., cov: 32)
• Consequence: MYO1E NM_004998.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393

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=-0.84).
• BP6: Variant 15-59137741-G-C is Benign according to our data. Variant chr15-59137741-G-C is described in ClinVar as [Benign]. Clinvar id is 1180130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1E	NM_004998.4	c.3251-285C>G		intron_variant		ENST00000288235.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1E	ENST00000288235.9	c.3251-285C>G		intron_variant		1	NM_004998.4	P1
MYO1E	ENST00000559412.1	c.129+551C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45537 AN: 151988 Hom.: 6998 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.300 AC: 45564 AN: 152106 Hom.: 7005 Cov.: 32 AF XY: 0.300 AC XY: 22328 AN XY: 74366

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.317

Alfa AF: 0.173 Hom.: 351

Bravo AF: 0.308

Asia WGS AF: 0.334 AC: 1160 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.21
Dann	Benign	0.29

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: rs56375269; hg19: chr15-59429940;