chr15-59136459-C-T

Variant names:

• chr15-59136459-C-T
• rs4218
• NM_004998.4:c.*921G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004998.4(MYO1E):​c.*921G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 129426 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71016

African (AFR) AF: 0.00 AC: 0 AN: 4316

American (AMR) AF: 0.00 AC: 0 AN: 9268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2994

East Asian (EAS) AF: 0.00 AC: 0 AN: 6758

South Asian (SAS) AF: 0.00 AC: 0 AN: 24328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 410

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 70240

Other (OTH) AF: 0.00 AC: 0 AN: 6120

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;