rs4987194

Variant names:

• chr15-52313664-A-G
• rs4987194
• ENST00000399228.6:n.*1367T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382347.1(MYO5A):​c.*32T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,612,714 control chromosomes in the GnomAD database, including 3,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (1755 hom., cov: 33)
  • Exomes 𝑓: 0.015 (1949 hom.)
• Consequence: MYO5A NM_001382347.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.776
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Griscelli syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Griscelli syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-52313664-A-G is Benign according to our data. Variant chr15-52313664-A-G is described in ClinVar as [Benign]. Clinvar id is 1280102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.*32T>C		3_prime_UTR_variant	Exon 42 of 42	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.*32T>C		3_prime_UTR_variant	Exon 42 of 42	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 13096 AN: 152044 Hom.: 1741 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.0569

GnomAD2 exomes AF: 0.0317 AC: 7903 AN: 249436 AF XY: 0.0292

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.0122

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.0176

Gnomad FIN exome AF: 0.000649

Gnomad NFE exome AF: 0.00374

Gnomad OTH exome AF: 0.0155

GnomAD4 exome AF: 0.0148 AC: 21630 AN: 1460552 Hom.: 1949 Cov.: 30 AF XY: 0.0153 AC XY: 11102 AN XY: 726688

African (AFR) AF: 0.308 AC: 10275 AN: 33398

American (AMR) AF: 0.0135 AC: 605 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00337 AC: 88 AN: 26134

East Asian (EAS) AF: 0.0213 AC: 847 AN: 39692

South Asian (SAS) AF: 0.0603 AC: 5200 AN: 86196

European-Finnish (FIN) AF: 0.000655 AC: 35 AN: 53406

Middle Eastern (MID) AF: 0.0232 AC: 132 AN: 5696

European-Non Finnish (NFE) AF: 0.00259 AC: 2879 AN: 1110966

Other (OTH) AF: 0.0260 AC: 1569 AN: 60346

GnomAD4 genome AF: 0.0864 AC: 13149 AN: 152162 Hom.: 1755 Cov.: 33 AF XY: 0.0838 AC XY: 6238 AN XY: 74418

African (AFR) AF: 0.289 AC: 11984 AN: 41452

American (AMR) AF: 0.0260 AC: 397 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5184

South Asian (SAS) AF: 0.0579 AC: 279 AN: 4822

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00343 AC: 233 AN: 68016

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0359 Hom.: 278

Bravo AF: 0.0972

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.61
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4987194; hg19: chr15-52605861;