rs183302379

Variant names:

• chr15-52364656-G-A
• rs183302379
• NM_001382347.1:c.3207C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-52364656-G-A
• chr15-52364656-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001382347.1(MYO5A):​c.3207C>T​(p.Leu1069Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,613,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.46
• Publications: 0 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: ClinGen, G2P, 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 15-52364656-G-A is Benign according to our data. Variant chr15-52364656-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.46 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000414 (63/152072) while in subpopulation EAS AF = 0.0106 (55/5178). AF 95% confidence interval is 0.00838. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	NM_001382347.1	MANE Select	c.3207C>T	p.Leu1069Leu	synonymous	Exon 24 of 42	NP_001369276.1
	MYO5A	NM_001382348.1		c.3279C>T	p.Leu1093Leu	synonymous	Exon 25 of 43	NP_001369277.1
	MYO5A	NM_001382349.1		c.3279C>T	p.Leu1093Leu	synonymous	Exon 25 of 42	NP_001369278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.3207C>T	p.Leu1069Leu	synonymous	Exon 24 of 42	ENSP00000382179.4
	MYO5A	ENST00000399231.8	TSL:1	c.3207C>T	p.Leu1069Leu	synonymous	Exon 24 of 41	ENSP00000382177.3
	MYO5A	ENST00000356338.11	TSL:1	c.3207C>T	p.Leu1069Leu	synonymous	Exon 24 of 41	ENSP00000348693.7

Frequencies

GnomAD3 genomes AF: 0.000415 AC: 63 AN: 151956 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000679 AC: 169 AN: 248906 AF XY: 0.000659

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00873

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000247 AC: 361 AN: 1461524 Hom.: 0 Cov.: 32 AF XY: 0.000232 AC XY: 169 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.000112 AC: 5 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00655 AC: 260 AN: 39666

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111778

Other (OTH) AF: 0.00111 AC: 67 AN: 60380

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.000498 AC XY: 37 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.000196 AC: 3 AN: 15286

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

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5178

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000446

Asia WGS AF: 0.00751 AC: 26 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.028
DANN	Benign	0.53
PhyloP100		-3.5
Mutation Taster		=98/2	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: rs183302379; hg19: chr15-52656853;