rs1724623

Variant names:

• chr15-52389376-A-G
• rs1724623
• NM_001382347.1:c.1543-13T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-52389376-A-G
• chr15-52389376-A-C
• chr15-52389376-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382347.1(MYO5A):​c.1543-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,602,854 control chromosomes in the GnomAD database, including 774,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (64826 hom., cov: 30)
  • Exomes 𝑓: 0.99 (709307 hom.)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.62
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-52389376-A-G is Benign according to our data. Variant chr15-52389376-A-G is described in ClinVar as Benign. ClinVar VariationId is 255639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 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.1543-13T>C		intron	N/A	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.1615-13T>C		intron	N/A	NP_001369277.1
	MYO5A	NM_001382349.1		c.1615-13T>C		intron	N/A	NP_001369278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.1543-13T>C		intron	N/A	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.1543-13T>C		intron	N/A	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.1543-13T>C		intron	N/A	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes AF: 0.933 AC: 139141 AN: 149212 Hom.: 64799 Cov.: 30

Gnomad AFR AF: 0.768

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.943

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.944

GnomAD2 exomes AF: 0.969 AC: 240664 AN: 248428 AF XY: 0.971

Gnomad AFR exome AF: 0.707

Gnomad AMR exome AF: 0.987

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 0.982

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.985

GnomAD4 exome AF: 0.988 AC: 1435844 AN: 1453544 Hom.: 709307 Cov.: 34 AF XY: 0.987 AC XY: 714208 AN XY: 723470

African (AFR) AF: 0.770 AC: 23700 AN: 30784

American (AMR) AF: 0.986 AC: 44007 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 26023 AN: 26094

East Asian (EAS) AF: 0.979 AC: 38746 AN: 39576

South Asian (SAS) AF: 0.945 AC: 80662 AN: 85394

European-Finnish (FIN) AF: 0.999 AC: 53264 AN: 53302

Middle Eastern (MID) AF: 0.982 AC: 5634 AN: 5738

European-Non Finnish (NFE) AF: 0.997 AC: 1105099 AN: 1107932

Other (OTH) AF: 0.977 AC: 58709 AN: 60100

GnomAD4 genome AF: 0.932 AC: 139215 AN: 149310 Hom.: 64826 Cov.: 30 AF XY: 0.934 AC XY: 68268 AN XY: 73068

African (AFR) AF: 0.768 AC: 29693 AN: 38676

American (AMR) AF: 0.976 AC: 14902 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3467 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5075 AN: 5182

South Asian (SAS) AF: 0.944 AC: 4533 AN: 4802

European-Finnish (FIN) AF: 1.00 AC: 10585 AN: 10590

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67788 AN: 68020

Other (OTH) AF: 0.943 AC: 1973 AN: 2092

Alfa AF: 0.966 Hom.: 13212

Bravo AF: 0.904

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.045
DANN	Benign	0.62
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs1724623; hg19: chr15-52681573;