Variant 15-59136664-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004998.4(MYO1E):c.*716A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 456,346 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 10 hom. )

Consequence

MYO1E
NM_004998.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.77

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-59136664-T-C is Benign according to our data. Variant chr15-59136664-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1712474.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-59136664-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00309 (471/152302) while in subpopulation SAS AF= 0.011 (53/4822). AF 95% confidence interval is 0.00863. There are 0 homozygotes in gnomad4. There are 227 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1E	NM_004998.4 linkuse as main transcript	c.*716A>G		3_prime_UTR_variant	28/28	ENST00000288235.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1E	ENST00000288235.9 linkuse as main transcript	c.*716A>G		3_prime_UTR_variant	28/28	1	NM_004998.4	P1
MYO1E	ENST00000559412.1 linkuse as main transcript	c.*21A>G		3_prime_UTR_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

473

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00521

AC:

711

AN:

136578

Hom.:

AF XY:

0.00588

AC XY:

436

AN XY:

74146

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.00274

Gnomad ASJ exome

AF:

0.00796

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.000930

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00591

AC:

1796

AN:

304044

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

1140

AN XY:

173164

show subpopulations

Gnomad4 AFR exome

AF:

0.000812

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00714

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.00117

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00429

GnomAD4 genome

AF:

0.00309

AC:

471

AN:

152302

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00429

Hom.:

Bravo

AF:

0.00297

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Kidney disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 16, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.75

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over