Variant rs185241256 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001382347.1(MYO5A):c.5409+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,608,486 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 55 hom. )

Consequence

MYO5A
NM_001382347.1 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.673

Variant links:

Genes affected

MYO5A (HGNC:7602): (myosin VA) This gene is one of three myosin V heavy-chain genes, belonging to the myosin gene superfamily. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. The protein encoded by this gene is abundant in melanocytes and nerve cells. Mutations in this gene cause Griscelli syndrome type-1 (GS1) and neuroectodermal melanolysosomal disease, or Elejalde disease. [provided by RefSeq, Sep 2023]

MYO5A 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=-0.82).

BP6

Variant 15-52317032-G-A is Benign according to our data. Variant chr15-52317032-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52317032-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0042 (639/152282) while in subpopulation NFE AF= 0.00647 (440/68022). AF 95% confidence interval is 0.00597. There are 2 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5A	NM_001382347.1 linkuse as main transcript	c.5409+16C>T		intron_variant		ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7 linkuse as main transcript	c.5409+16C>T		intron_variant		5	NM_001382347.1	ENSP00000382179		Q9Y4I1-3

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

638

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00490

AC:

1221

AN:

249350

Hom.:

AF XY:

0.00544

AC XY:

736

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00951

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00608

Gnomad OTH exome

AF:

0.00595

GnomAD4 exome

AF:

0.00639

AC:

9311

AN:

1456204

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

4760

AN XY:

724862

show subpopulations

Gnomad4 AFR exome

AF:

0.000660

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00935

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00676

Gnomad4 OTH exome

AF:

0.00744

GnomAD4 genome

AF:

0.00420

AC:

639

AN:

152282

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00647

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00540

Hom.:

Bravo

AF:

0.00420

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.62

DANN

Benign

0.25

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