NM_004998.4:c.4-45105A>C

Variant names:

• chr15-59317554-T-G
• rs10851648
• NM_004998.4:c.4-45105A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 6

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYO1E	NM_004998.4	c.4-45105A>C		intron_variant	Intron 1 of 27	ENST00000288235.9	NP_004989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1E	ENST00000288235.9	c.4-45105A>C		intron_variant	Intron 1 of 27	1	NM_004998.4	ENSP00000288235.4
MYO1E	ENST00000558571.1	n.4-45105A>C		intron_variant	Intron 1 of 5	5		ENSP00000453811.1
MYO1E	ENST00000558646.1	n.375-45105A>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.552 AC: 22882 AN: 41434

American (AMR) AF: 0.799 AC: 12218 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3081 AN: 3472

East Asian (EAS) AF: 0.509 AC: 2623 AN: 5152

South Asian (SAS) AF: 0.754 AC: 3642 AN: 4828

European-Finnish (FIN) AF: 0.670 AC: 7085 AN: 10572

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56203 AN: 67956

Other (OTH) AF: 0.745 AC: 1571 AN: 2110

Alfa AF: 0.801 Hom.: 27545

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10851648; hg19: chr15-59609753;