NM_001382347.1:c.2814G>A

Variant names:

• chr15-52372127-C-T
• rs190656197
• NM_001382347.1:c.2814G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001382347.1(MYO5A):​c.2814G>A​(p.Glu938Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,613,618 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (26 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.329
• Publications: 1 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: G2P, ClinGen, 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 15-52372127-C-T is Benign according to our data. Variant chr15-52372127-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.329 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0038 (579/152312) while in subpopulation NFE AF = 0.00656 (446/68028). AF 95% confidence interval is 0.00605. There are 3 homozygotes in GnomAd4. There are 285 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.2814G>A	p.Glu938Glu	synonymous	Exon 21 of 42	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.2886G>A	p.Glu962Glu	synonymous	Exon 22 of 43	NP_001369277.1
	MYO5A	NM_001382349.1		c.2886G>A	p.Glu962Glu	synonymous	Exon 22 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.2814G>A	p.Glu938Glu	synonymous	Exon 21 of 42	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.2814G>A	p.Glu938Glu	synonymous	Exon 21 of 41	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.2814G>A	p.Glu938Glu	synonymous	Exon 21 of 41	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes AF: 0.00380 AC: 579 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00656

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00339 AC: 845 AN: 249006 AF XY: 0.00345

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00561

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00553 AC: 8084 AN: 1461306 Hom.: 26 Cov.: 31 AF XY: 0.00544 AC XY: 3956 AN XY: 726942

African (AFR) AF: 0.00102 AC: 34 AN: 33462

American (AMR) AF: 0.00208 AC: 93 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00208 AC: 179 AN: 86230

European-Finnish (FIN) AF: 0.00172 AC: 92 AN: 53420

Middle Eastern (MID) AF: 0.000376 AC: 2 AN: 5326

European-Non Finnish (NFE) AF: 0.00671 AC: 7458 AN: 1111974

Other (OTH) AF: 0.00368 AC: 222 AN: 60342

GnomAD4 genome AF: 0.00380 AC: 579 AN: 152312 Hom.: 3 Cov.: 32 AF XY: 0.00383 AC XY: 285 AN XY: 74472

African (AFR) AF: 0.00140 AC: 58 AN: 41566

American (AMR) AF: 0.00209 AC: 32 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4828

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00656 AC: 446 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00485 Hom.: 2

Bravo AF: 0.00355

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.3
DANN	Benign	0.51
PhyloP100		0.33
Mutation Taster		=73/27	polymorphism

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: rs190656197; hg19: chr15-52664324;