15-52319154-C-A

Variant names:

• chr15-52319154-C-A
• rs143298463
• NM_001382347.1:c.5140G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001382347.1(MYO5A):​c.5140G>T​(p.Val1714Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1714I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO5A NM_001382347.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 8 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Griscelli syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382347.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	NM_001382347.1	MANE Select	c.5140G>T	p.Val1714Phe	missense	Exon 39 of 42	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.5212G>T	p.Val1738Phe	missense	Exon 40 of 43	NP_001369277.1
	MYO5A	NM_001382349.1		c.5137G>T	p.Val1713Phe	missense	Exon 39 of 42	NP_001369278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.5140G>T	p.Val1714Phe	missense	Exon 39 of 42	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.5065G>T	p.Val1689Phe	missense	Exon 38 of 41	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.5059G>T	p.Val1687Phe	missense	Exon 38 of 41	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	-0.015	N
PhyloP100		6.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.16	N
REVEL	Uncertain	0.55
Sift	Benign	0.73	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.75
MutPred		0.73		Loss of catalytic residue at Q1687 (P = 0.0824)
MVP		0.81
MPC		1.2
ClinPred		0.81	D
GERP RS		4.6
Varity_R		0.43
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143298463; hg19: chr15-52611351;