rs143298463

Positions:

• chr15-52319154-C-A
• chr15-52319154-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO5A NM_001382347.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYO5A. . Gene score misZ 3.0961 (greater than the threshold 3.09). Trascript score misZ 5.1368 (greater than threshold 3.09). GenCC has associacion of gene with Griscelli syndrome type 3, Griscelli syndrome type 1.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.5140G>T	p.Val1714Phe	missense_variant	39/42	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.5140G>T	p.Val1714Phe	missense_variant	39/42	5	NM_001382347.1	ENSP00000382179

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;T;.;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	-0.015	N;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.16	N;N;.;.;.;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.73	T;T;.;.;.;T;T
Sift4G	Benign	0.78	T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;.;.;.
Vest4		0.75
MutPred		0.73		Loss of catalytic residue at Q1687 (P = 0.0824);.;.;Loss of catalytic residue at Q1687 (P = 0.0824);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

Publications

LitVar

Other links and lift over

dbSNP: rs143298463; hg19: chr15-52611351;