NM_001382347.1:c.5040T>C

Variant names:

• chr15-52319254-A-G
• rs2290332
• NM_001382347.1:c.5040T>C

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.5040T>C​(p.Asp1680Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,613,882 control chromosomes in the GnomAD database, including 32,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3977 hom., cov: 32)
  • Exomes 𝑓: 0.17 (28297 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.49
• Publications: 22 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-52319254-A-G is Benign according to our data. Variant chr15-52319254-A-G is described in ClinVar as Benign. ClinVar VariationId is 255655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

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.5040T>C	p.Asp1680Asp	synonymous	Exon 39 of 42	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.5112T>C	p.Asp1704Asp	synonymous	Exon 40 of 43	NP_001369277.1
	MYO5A	NM_001382349.1		c.5037T>C	p.Asp1679Asp	synonymous	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.5040T>C	p.Asp1680Asp	synonymous	Exon 39 of 42	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.4965T>C	p.Asp1655Asp	synonymous	Exon 38 of 41	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.4959T>C	p.Asp1653Asp	synonymous	Exon 38 of 41	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30963 AN: 151924 Hom.: 3977 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.227 AC: 56554 AN: 249560 AF XY: 0.226

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.601

Gnomad FIN exome AF: 0.0705

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.172 AC: 251218 AN: 1461840 Hom.: 28297 Cov.: 34 AF XY: 0.177 AC XY: 128617 AN XY: 727228

African (AFR) AF: 0.275 AC: 9220 AN: 33480

American (AMR) AF: 0.276 AC: 12335 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6511 AN: 26136

East Asian (EAS) AF: 0.577 AC: 22905 AN: 39700

South Asian (SAS) AF: 0.351 AC: 30307 AN: 86258

European-Finnish (FIN) AF: 0.0761 AC: 4064 AN: 53416

Middle Eastern (MID) AF: 0.189 AC: 1092 AN: 5768

European-Non Finnish (NFE) AF: 0.138 AC: 152936 AN: 1111964

Other (OTH) AF: 0.196 AC: 11848 AN: 60394

GnomAD4 genome AF: 0.204 AC: 30982 AN: 152042 Hom.: 3977 Cov.: 32 AF XY: 0.206 AC XY: 15310 AN XY: 74338

African (AFR) AF: 0.270 AC: 11190 AN: 41426

American (AMR) AF: 0.225 AC: 3437 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3468

East Asian (EAS) AF: 0.572 AC: 2952 AN: 5160

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4820

European-Finnish (FIN) AF: 0.0653 AC: 692 AN: 10600

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9562 AN: 67976

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.168 Hom.: 3800

Bravo AF: 0.216

Asia WGS AF: 0.497 AC: 1726 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.139

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.40
PhyloP100		-2.5
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2290332; hg19: chr15-52611451; COSMIC: COSV62558116; COSMIC: COSV62558116;