15-52397434-T-G

Variant names:

• chr15-52397434-T-G
• rs1724577
• NM_001382347.1:c.1086A>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382347.1(MYO5A):​c.1086A>C​(p.Glu362Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,613,964 control chromosomes in the GnomAD database, including 776,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64899 hom., cov: 31)
  • Exomes 𝑓: 0.99 (711837 hom.)
• Consequence: MYO5A NM_001382347.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.136

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2907003E-6).
• BP6: Variant 15-52397434-T-G is Benign according to our data. Variant chr15-52397434-T-G is described in ClinVar as [Benign]. Clinvar id is 1321831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52397434-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.1086A>C	p.Glu362Asp	missense_variant	Exon 10 of 42	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.1086A>C	p.Glu362Asp	missense_variant	Exon 10 of 42	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139254 AN: 152086 Hom.: 64873 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.939

GnomAD3 exomes AF: 0.969 AC: 241352 AN: 249110 Hom.: 117545 AF XY: 0.971 AC XY: 131235 AN XY: 135158

Gnomad AFR exome AF: 0.709

Gnomad AMR exome AF: 0.987

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 0.982

Gnomad SAS exome AF: 0.936

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.985

GnomAD4 exome AF: 0.986 AC: 1440945 AN: 1461760 Hom.: 711837 Cov.: 57 AF XY: 0.985 AC XY: 716463 AN XY: 727186

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.986

Gnomad4 ASJ exome AF: 0.997

Gnomad4 EAS exome AF: 0.979

Gnomad4 SAS exome AF: 0.940

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.975

GnomAD4 genome AF: 0.915 AC: 139327 AN: 152204 Hom.: 64899 Cov.: 31 AF XY: 0.918 AC XY: 68324 AN XY: 74424

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.936

Alfa AF: 0.981 Hom.: 145076

Bravo AF: 0.905

TwinsUK AF: 0.997 AC: 3696

ALSPAC AF: 0.996 AC: 3838

ESP6500AA AF: 0.729 AC: 2881

ESP6500EA AF: 0.996 AC: 8301

ExAC AF: 0.963 AC: 116326

Asia WGS AF: 0.932 AC: 3237 AN: 3476

EpiCase AF: 0.996

EpiControl AF: 0.997

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Griscelli syndrome type 1 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.2
DANN	Benign	0.82
DEOGEN2	Benign	0.23	T;.;T;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.21	T;T;T;T;T;T
MetaRNN	Benign	0.0000013	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.82	L;L;.;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.010	N;N;.;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.70	T;T;.;T;T;T
Sift4G	Benign	0.96	T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.099
MutPred		0.47		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MPC		0.34
ClinPred		0.00070	T
GERP RS		-4.7
Varity_R		0.069
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1724577; hg19: chr15-52689631; COSMIC: COSV62562968; COSMIC: COSV62562968;