rs16964944

chr15-52384195-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BA1

The NM_001382347.1(MYO5A):c.1880T>C(p.Met627Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,614,044 control chromosomes in the GnomAD database, including 1,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.053 (620 hom., cov: 32)
  • Exomes 𝑓: 0.011 (837 hom.)
• Consequence: MYO5A NM_001382347.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.890

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 -19 ACMG points.

• PP2: Missense variant where missense usually causes diseases, MYO5A
• BP4: Computational evidence support a benign effect (MetaRNN=0.0010196269).
• BP6: Variant 15-52384195-A-G is Benign according to our data. Variant chr15-52384195-A-G is described in ClinVar as [Benign]. Clinvar id is 255640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52384195-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.1880T>C	p.Met627Thr	missense_variant	15/42	ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.1880T>C	p.Met627Thr	missense_variant	15/42	5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8038 AN: 152072 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.0336

GnomAD3 exomes AF: 0.0232 AC: 5794 AN: 249480 Hom.: 334 AF XY: 0.0231 AC XY: 3128 AN XY: 135352

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.00802

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.0178

Gnomad SAS exome AF: 0.0641

Gnomad FIN exome AF: 0.000649

Gnomad NFE exome AF: 0.00352

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0113 AC: 16456 AN: 1461854 Hom.: 837 Cov.: 31 AF XY: 0.0122 AC XY: 8895 AN XY: 727232

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.00865

Gnomad4 ASJ exome AF: 0.00275

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.0601

Gnomad4 FIN exome AF: 0.000655

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome AF: 0.0529 AC: 8058 AN: 152190 Hom.: 620 Cov.: 32 AF XY: 0.0517 AC XY: 3851 AN XY: 74424

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00145

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.0581

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00306

Gnomad4 OTH AF: 0.0370

Alfa AF: 0.0133 Hom.: 265

Bravo AF: 0.0591

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.161 AC: 657

ESP6500EA AF: 0.00407 AC: 34

ExAC AF: 0.0276 AC: 3334

Asia WGS AF: 0.0610 AC: 215 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	1.5
Dann	Benign	0.29
DEOGEN2	Benign	0.19	T;.;T;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.70	T;T;T;T;T;T
MetaRNN	Benign	0.0010	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.1	N;N;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.18	N;N;.;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.82	T;T;.;T;T;T
Sift4G	Benign	0.87	T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.011
MPC		0.43
ClinPred		0.0041	T
GERP RS		-2.2
Varity_R		0.029
gMVP		0.14

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: rs16964944; hg19: chr15-52676392;