rs143400779

chr15-52340176-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001382347.1(MYO5A):c.4239+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,613,768 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (8 hom.)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.544

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-52340176-G-A is Benign according to our data. Variant chr15-52340176-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52340176-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00215 (328/152288) while in subpopulation NFE AF= 0.0036 (245/67998). AF 95% confidence interval is 0.00323. There are 0 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.4239+20C>T		intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.4239+20C>T		intron_variant		5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00360

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00191 AC: 473 AN: 247802 Hom.: 2 AF XY: 0.00194 AC XY: 261 AN XY: 134602

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000898

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000981

Gnomad FIN exome AF: 0.00186

Gnomad NFE exome AF: 0.00314

Gnomad OTH exome AF: 0.00314

GnomAD4 exome AF: 0.00242 AC: 3543 AN: 1461480 Hom.: 8 Cov.: 31 AF XY: 0.00248 AC XY: 1801 AN XY: 727086

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.00191

Gnomad4 NFE exome AF: 0.00286

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00215 AC: 328 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.00201 AC XY: 150 AN XY: 74474

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00360

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00175

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.1
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs143400779; hg19: chr15-52632373;