rs11637651

Variant names:

• chr15-52372211-G-A
• rs11637651
• NM_001382347.1:c.2730C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-52372211-G-A
• chr15-52372211-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001382347.1(MYO5A):​c.2730C>T​(p.Ile910Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,613,460 control chromosomes in the GnomAD database, including 3,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (238 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3545 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.643
• Publications: 10 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 15-52372211-G-A is Benign according to our data. Variant chr15-52372211-G-A is described in ClinVar as Benign. ClinVar VariationId is 255642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.643 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.085 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.2730C>T	p.Ile910Ile	synonymous	Exon 21 of 42	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.2802C>T	p.Ile934Ile	synonymous	Exon 22 of 43	NP_001369277.1
	MYO5A	NM_001382349.1		c.2802C>T	p.Ile934Ile	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.2730C>T	p.Ile910Ile	synonymous	Exon 21 of 42	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.2730C>T	p.Ile910Ile	synonymous	Exon 21 of 41	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.2730C>T	p.Ile910Ile	synonymous	Exon 21 of 41	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7829 AN: 152106 Hom.: 237 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0517

GnomAD2 exomes AF: 0.0578 AC: 14393 AN: 248954 AF XY: 0.0615

Gnomad AFR exome AF: 0.0310

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.0714

Gnomad FIN exome AF: 0.0260

Gnomad NFE exome AF: 0.0669

Gnomad OTH exome AF: 0.0575

GnomAD4 exome AF: 0.0666 AC: 97256 AN: 1461236 Hom.: 3545 Cov.: 32 AF XY: 0.0677 AC XY: 49182 AN XY: 726940

African (AFR) AF: 0.0291 AC: 975 AN: 33466

American (AMR) AF: 0.0286 AC: 1281 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0281 AC: 734 AN: 26136

East Asian (EAS) AF: 0.0670 AC: 2659 AN: 39698

South Asian (SAS) AF: 0.0943 AC: 8128 AN: 86220

European-Finnish (FIN) AF: 0.0275 AC: 1469 AN: 53334

Middle Eastern (MID) AF: 0.0647 AC: 345 AN: 5334

European-Non Finnish (NFE) AF: 0.0699 AC: 77772 AN: 1111984

Other (OTH) AF: 0.0645 AC: 3893 AN: 60348

GnomAD4 genome AF: 0.0515 AC: 7840 AN: 152224 Hom.: 238 Cov.: 32 AF XY: 0.0494 AC XY: 3675 AN XY: 74440

African (AFR) AF: 0.0305 AC: 1266 AN: 41524

American (AMR) AF: 0.0383 AC: 586 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 96 AN: 3472

East Asian (EAS) AF: 0.0757 AC: 392 AN: 5178

South Asian (SAS) AF: 0.0920 AC: 444 AN: 4824

European-Finnish (FIN) AF: 0.0205 AC: 217 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4624 AN: 68010

Other (OTH) AF: 0.0526 AC: 111 AN: 2112

Alfa AF: 0.0567 Hom.: 126

Bravo AF: 0.0502

Asia WGS AF: 0.0670 AC: 233 AN: 3478

EpiCase AF: 0.0661

EpiControl AF: 0.0669

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	-0.36
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.64
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: rs11637651; hg19: chr15-52664408; COSMIC: COSV62558141;