NM_004998.4:c.1699-164G>C

Variant names:

• chr15-59195731-C-G
• rs2306786
• NM_004998.4:c.1699-164G>C

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.1699-164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,248 control chromosomes in the GnomAD database, including 561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.081 (561 hom., cov: 32)
• Consequence: MYO1E NM_004998.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.240
• Publications: 10 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=-0.82).
• BP6: Variant 15-59195731-C-G is Benign according to our data. Variant chr15-59195731-C-G is described in ClinVar as Benign. ClinVar VariationId is 1248737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0995 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1E	NM_004998.4	MANE Select	c.1699-164G>C		intron	N/A	NP_004989.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1E	ENST00000288235.9	TSL:1 MANE Select	c.1699-164G>C		intron	N/A	ENSP00000288235.4
	MYO1E	ENST00000560749.1	TSL:3	c.268-164G>C		intron	N/A	ENSP00000454113.1
	MYO1E	ENST00000559269.5	TSL:5	c.597+22160G>C		intron	N/A	ENSP00000453232.1

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12288 AN: 152130 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.0807 AC: 12284 AN: 152248 Hom.: 561 Cov.: 32 AF XY: 0.0805 AC XY: 5995 AN XY: 74452

African (AFR) AF: 0.0427 AC: 1774 AN: 41542

American (AMR) AF: 0.104 AC: 1587 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5186

South Asian (SAS) AF: 0.0969 AC: 468 AN: 4830

European-Finnish (FIN) AF: 0.0842 AC: 892 AN: 10596

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0954 AC: 6486 AN: 68010

Other (OTH) AF: 0.0927 AC: 196 AN: 2114

Alfa AF: 0.0874 Hom.: 100

Bravo AF: 0.0813

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		-0.24
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: rs2306786; hg19: chr15-59487930;