chr15-59317554-T-G

Position:

• chr15-59317554-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004998.4(MYO1E):​c.4-45105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,016 control chromosomes in the GnomAD database, including 41,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (41326 hom., cov: 31)
• Consequence: MYO1E NM_004998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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]

MYO1E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1E	NM_004998.4	c.4-45105A>C		intron_variant		ENST00000288235.9	NP_004989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1E	ENST00000288235.9	c.4-45105A>C		intron_variant		1	NM_004998.4	ENSP00000288235.4
MYO1E	ENST00000558571.1	n.4-45105A>C		intron_variant		5		ENSP00000453811.1
MYO1E	ENST00000558646.1	n.375-45105A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110307 AN: 151900 Hom.: 41313 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.726 AC: 110363 AN: 152016 Hom.: 41326 Cov.: 31 AF XY: 0.720 AC XY: 53522 AN XY: 74304

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.745

Alfa AF: 0.799 Hom.: 24916

Bravo AF: 0.729

Asia WGS AF: 0.600 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.46

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: rs10851648; hg19: chr15-59609753;