Variant chr15-59138114-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.197

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 -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 id is 1220943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-59138114-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1E	NM_004998.4 linkuse as main transcript	c.3250+84G>T		intron_variant		ENST00000288235.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1E	ENST00000288235.9 linkuse as main transcript	c.3250+84G>T		intron_variant		1	NM_004998.4	P1
MYO1E	ENST00000559412.1 linkuse as main transcript	c.129+178G>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0380

AC:

5790

AN:

152172

Hom.:

240

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0201

Gnomad4 ASJ exome

AF:

0.0356

Gnomad4 EAS exome

AF:

0.0445

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.0512

Gnomad4 NFE exome

AF:

0.00450

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.0381

AC:

5802

AN:

152290

Hom.:

242

Cov.:

AF XY:

0.0396

AC XY:

2951

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0984

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0360

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0528

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0263

Hom.:

Bravo

AF:

0.0385

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 15, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.3

DANN

Benign

0.40

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