rs8041633

Variant names:

• chr15-59137272-T-G
• rs8041633
• NM_004998.4:c.*108A>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.*108A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 1,027,896 control chromosomes in the GnomAD database, including 591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (266 hom., cov: 32)
  • Exomes 𝑓: 0.021 (325 hom.)
• Consequence: MYO1E NM_004998.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.112
• Publications: 3 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=-0.79).
• BP6: Variant 15-59137272-T-G is Benign according to our data. Variant chr15-59137272-T-G is described in ClinVar as Benign. ClinVar VariationId is 1267843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.*108A>C		3_prime_UTR	Exon 28 of 28	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.*108A>C		3_prime_UTR	Exon 28 of 28	ENSP00000288235.4	Q12965
	MYO1E	ENST00000884343.1		c.*108A>C		3_prime_UTR	Exon 28 of 28	ENSP00000554402.1
	MYO1E	ENST00000884345.1		c.*108A>C		3_prime_UTR	Exon 28 of 28	ENSP00000554404.1

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6580 AN: 152070 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0210 AC: 18432 AN: 875708 Hom.: 325 Cov.: 12 AF XY: 0.0200 AC XY: 9142 AN XY: 456094

African (AFR) AF: 0.109 AC: 2400 AN: 22028

American (AMR) AF: 0.0209 AC: 826 AN: 39498

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 437 AN: 21956

East Asian (EAS) AF: 0.00777 AC: 282 AN: 36292

South Asian (SAS) AF: 0.00627 AC: 451 AN: 71922

European-Finnish (FIN) AF: 0.00659 AC: 327 AN: 49584

Middle Eastern (MID) AF: 0.0304 AC: 106 AN: 3492

European-Non Finnish (NFE) AF: 0.0211 AC: 12454 AN: 589868

Other (OTH) AF: 0.0280 AC: 1149 AN: 41068

GnomAD4 genome AF: 0.0434 AC: 6606 AN: 152188 Hom.: 266 Cov.: 32 AF XY: 0.0422 AC XY: 3139 AN XY: 74420

African (AFR) AF: 0.107 AC: 4418 AN: 41480

American (AMR) AF: 0.0298 AC: 456 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3468

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5180

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4820

European-Finnish (FIN) AF: 0.00555 AC: 59 AN: 10622

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1383 AN: 68012

Other (OTH) AF: 0.0412 AC: 87 AN: 2112

Alfa AF: 0.0296 Hom.: 59

Bravo AF: 0.0487

Asia WGS AF: 0.0160 AC: 56 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	-0.79
CADD	Benign	7.7
DANN	Benign	0.67
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8041633; hg19: chr15-59429471;