Variant rs117029104 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.2817+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 1,613,506 control chromosomes in the GnomAD database, including 700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 37 hom., cov: 32)

Exomes 𝑓: 0.027 ( 663 hom. )

Consequence

MYO5A
NM_001382347.1 splice_donor_region, intron

Scores

Splicing: ADA: 0.0004716

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00300

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=-0.66).

BP6

Variant 15-52372121-C-T is Benign according to our data. Variant chr15-52372121-C-T is described in ClinVar as [Benign]. Clinvar id is 255644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0193 (2934/152286) while in subpopulation NFE AF= 0.0288 (1962/68034). AF 95% confidence interval is 0.0278. There are 37 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5A	NM_001382347.1 linkuse as main transcript	c.2817+3G>A		splice_donor_region_variant, 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.2817+3G>A		splice_donor_region_variant, intron_variant		5	NM_001382347.1	ENSP00000382179		Q9Y4I1-3

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2933

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00579

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0186

AC:

4638

AN:

248934

Hom.:

AF XY:

0.0183

AC XY:

2476

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.00478

Gnomad AMR exome

AF:

0.00794

Gnomad ASJ exome

AF:

0.00607

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00539

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.0276

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0273

AC:

39942

AN:

1461220

Hom.:

663

Cov.:

AF XY:

0.0265

AC XY:

19295

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00475

Gnomad4 AMR exome

AF:

0.00843

Gnomad4 ASJ exome

AF:

0.00562

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00565

Gnomad4 FIN exome

AF:

0.0394

Gnomad4 NFE exome

AF:

0.0317

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.0193

AC:

2934

AN:

152286

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1418

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0288

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0170

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0257

EpiControl

AF:

0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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

-0.66

CADD

Benign

3.7

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00047

dbscSNV1_RF

Benign

0.050

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