chr15-59138114-C-A

Variant names:

• chr15-59138114-C-A
• rs56294483
• NM_004998.4:c.3250+84G>T

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.3250+84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,537,582 control chromosomes in the GnomAD database, including 603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (242 hom., cov: 32)
  • Exomes 𝑓: 0.012 (361 hom.)
• Consequence: MYO1E NM_004998.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.197
• 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=-0.77).
• BP6: Variant 15-59138114-C-A is Benign according to our data. Variant chr15-59138114-C-A is described in ClinVar as Benign. ClinVar VariationId is 1220943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0959 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.3250+84G>T		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+84G>T		intron	N/A	ENSP00000288235.4	Q12965
	MYO1E	ENST00000884343.1		c.3283+84G>T		intron	N/A	ENSP00000554402.1
	MYO1E	ENST00000884345.1		c.3223+84G>T		intron	N/A	ENSP00000554404.1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5790 AN: 152172 Hom.: 240 Cov.: 32

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.0117 AC: 16168 AN: 1385292 Hom.: 361 AF XY: 0.0112 AC XY: 7790 AN XY: 693438

African (AFR) AF: 0.103 AC: 3291 AN: 31870

American (AMR) AF: 0.0201 AC: 897 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.0356 AC: 916 AN: 25710

East Asian (EAS) AF: 0.0445 AC: 1750 AN: 39366

South Asian (SAS) AF: 0.0118 AC: 997 AN: 84252

European-Finnish (FIN) AF: 0.0512 AC: 2467 AN: 48158

Middle Eastern (MID) AF: 0.0210 AC: 118 AN: 5626

European-Non Finnish (NFE) AF: 0.00450 AC: 4714 AN: 1047668

Other (OTH) AF: 0.0175 AC: 1018 AN: 58020

GnomAD4 genome AF: 0.0381 AC: 5802 AN: 152290 Hom.: 242 Cov.: 32 AF XY: 0.0396 AC XY: 2951 AN XY: 74460

African (AFR) AF: 0.0984 AC: 4091 AN: 41560

American (AMR) AF: 0.0179 AC: 274 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.0360 AC: 187 AN: 5190

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4830

European-Finnish (FIN) AF: 0.0528 AC: 560 AN: 10600

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00629 AC: 428 AN: 68020

Other (OTH) AF: 0.0289 AC: 61 AN: 2110

Alfa AF: 0.0301 Hom.: 26

Bravo AF: 0.0385

Asia WGS AF: 0.0370 AC: 127 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	-0.77
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.20
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: rs56294483; hg19: chr15-59430313;