rs13329278

Variant names:

• chr15-52359977-T-C
• rs13329278
• NM_001382347.1:c.3414A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001382347.1(MYO5A):​c.3414A>G​(p.Ser1138Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,605,090 control chromosomes in the GnomAD database, including 4,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (2246 hom., cov: 32)
  • Exomes 𝑓: 0.017 (2428 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.24
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-52359977-T-C is Benign according to our data. Variant chr15-52359977-T-C is described in ClinVar as Benign. ClinVar VariationId is 255647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.3414A>G	p.Ser1138Ser	synonymous_variant	Exon 25 of 42	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.3414A>G	p.Ser1138Ser	synonymous_variant	Exon 25 of 42	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14746 AN: 152138 Hom.: 2223 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00340

Gnomad OTH AF: 0.0617

GnomAD2 exomes AF: 0.0351 AC: 8712 AN: 247932 AF XY: 0.0322

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.00340

Gnomad EAS exome AF: 0.0255

Gnomad FIN exome AF: 0.000652

Gnomad NFE exome AF: 0.00379

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.0165 AC: 23997 AN: 1452834 Hom.: 2428 Cov.: 30 AF XY: 0.0168 AC XY: 12170 AN XY: 723206

African (AFR) AF: 0.347 AC: 11489 AN: 33154

American (AMR) AF: 0.0153 AC: 684 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00342 AC: 89 AN: 26036

East Asian (EAS) AF: 0.0338 AC: 1338 AN: 39620

South Asian (SAS) AF: 0.0642 AC: 5508 AN: 85850

European-Finnish (FIN) AF: 0.000657 AC: 35 AN: 53304

Middle Eastern (MID) AF: 0.0249 AC: 143 AN: 5740

European-Non Finnish (NFE) AF: 0.00260 AC: 2872 AN: 1104450

Other (OTH) AF: 0.0306 AC: 1839 AN: 60074

GnomAD4 genome AF: 0.0973 AC: 14817 AN: 152256 Hom.: 2246 Cov.: 32 AF XY: 0.0949 AC XY: 7062 AN XY: 74450

African (AFR) AF: 0.326 AC: 13532 AN: 41504

American (AMR) AF: 0.0291 AC: 446 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.0282 AC: 146 AN: 5186

South Asian (SAS) AF: 0.0616 AC: 297 AN: 4822

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00340 AC: 231 AN: 68030

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0408 Hom.: 2511

Bravo AF: 0.110

Asia WGS AF: 0.0850 AC: 295 AN: 3478

EpiCase AF: 0.00398

EpiControl AF: 0.00351

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		-1.2
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13329278; hg19: chr15-52652174;