NM_004998.4:c.3250+19_3250+26delGGCTGGGA

Variant names:

• chr15-59138171-GTCCCAGCC-G
• rs2079384813
• NM_004998.4:c.3250+19_3250+26delGGCTGGGA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_004998.4(MYO1E):​c.3250+19_3250+26delGGCTGGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO1E NM_004998.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-59138171-GTCCCAGCC-G is Benign according to our data. Variant chr15-59138171-GTCCCAGCC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1899713.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3250+19_3250+26delGGCTGGGA		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.3250+19_3250+26delGGCTGGGA		intron	N/A	ENSP00000288235.4	Q12965
	MYO1E	ENST00000884343.1		c.3283+19_3283+26delGGCTGGGA		intron	N/A	ENSP00000554402.1
	MYO1E	ENST00000884345.1		c.3223+19_3223+26delGGCTGGGA		intron	N/A	ENSP00000554404.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2079384813; hg19: chr15-59430370;