chr15-59136459-C-G

Variant names:

• chr15-59136459-C-G
• rs4218
• NM_004998.4:c.*921G>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.*921G>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 0.347 in 280,854 control chromosomes in the GnomAD database, including 17,653 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 0.37 (10519 hom., cov: 31)
  • Exomes 𝑓: 0.32 (7134 hom.)
• Consequence: MYO1E NM_004998.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 17 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1E	NM_004998.4	c.*921G>C		3_prime_UTR_variant	Exon 28 of 28	ENST00000288235.9	NP_004989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1E	ENST00000288235.9	c.*921G>C		3_prime_UTR_variant	Exon 28 of 28	1	NM_004998.4	ENSP00000288235.4
MYO1E	ENST00000559412.1	c.*226G>C		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000453936.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55975 AN: 151738 Hom.: 10501 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.321 AC: 41396 AN: 128996 Hom.: 7134 Cov.: 0 AF XY: 0.315 AC XY: 22283 AN XY: 70778

African (AFR) AF: 0.432 AC: 1856 AN: 4298

American (AMR) AF: 0.464 AC: 4292 AN: 9248

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1053 AN: 2986

East Asian (EAS) AF: 0.442 AC: 2975 AN: 6730

South Asian (SAS) AF: 0.247 AC: 5993 AN: 24264

European-Finnish (FIN) AF: 0.311 AC: 1546 AN: 4970

Middle Eastern (MID) AF: 0.373 AC: 150 AN: 402

European-Non Finnish (NFE) AF: 0.308 AC: 21561 AN: 69994

Other (OTH) AF: 0.323 AC: 1970 AN: 6104

GnomAD4 genome AF: 0.369 AC: 56035 AN: 151858 Hom.: 10519 Cov.: 31 AF XY: 0.368 AC XY: 27338 AN XY: 74202

African (AFR) AF: 0.446 AC: 18455 AN: 41378

American (AMR) AF: 0.429 AC: 6550 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2323 AN: 5156

South Asian (SAS) AF: 0.263 AC: 1263 AN: 4806

European-Finnish (FIN) AF: 0.317 AC: 3346 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21713 AN: 67932

Other (OTH) AF: 0.369 AC: 778 AN: 2108

Alfa AF: 0.344 Hom.: 1115

Bravo AF: 0.384

Asia WGS AF: 0.391 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4218; hg19: chr15-59428658; COSMIC: COSV55694936; COSMIC: COSV55694936;