15-59137741-G-C

Variant names:

• chr15-59137741-G-C
• rs56375269
• NM_004998.4:c.3251-285C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.393
• Publications: 2 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 -20 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 VariationId is 1180130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004998.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1E	NM_004998.4	MANE Select	c.3251-285C>G		intron	N/A	NP_004989.2	Q4KMR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1E	ENST00000288235.9	TSL:1 MANE Select	c.3251-285C>G		intron	N/A	ENSP00000288235.4	Q12965
	MYO1E	ENST00000884343.1		c.3284-285C>G		intron	N/A	ENSP00000554402.1
	MYO1E	ENST00000884345.1		c.3224-285C>G		intron	N/A	ENSP00000554404.1

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

African (AFR) AF: 0.242 AC: 10043 AN: 41484

American (AMR) AF: 0.392 AC: 5993 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2140 AN: 5168

South Asian (SAS) AF: 0.240 AC: 1160 AN: 4830

European-Finnish (FIN) AF: 0.299 AC: 3163 AN: 10582

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20845 AN: 67970

Other (OTH) AF: 0.317 AC: 668 AN: 2110

Alfa AF: 0.173 Hom.: 351

Bravo AF: 0.308

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.21
DANN	Benign	0.29
PhyloP100		0.39
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: rs56375269; hg19: chr15-59429940; COSMIC: COSV107299537; COSMIC: COSV107299537;