15-52407386-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001382347.1(MYO5A):c.852C>G(p.Asn284Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.653

Publications

1 publications found

Variant links:

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

MYO5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053923905).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000256 (39/152068) while in subpopulation AFR AF = 0.000942 (39/41400). AF 95% confidence interval is 0.000708. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO5A	NM_001382347.1	MANE Select	c.852C>G	p.Asn284Lys	missense	Exon 8 of 42	NP_001369276.1
MYO5A	NM_001382348.1		c.924C>G	p.Asn308Lys	missense	Exon 9 of 43	NP_001369277.1
MYO5A	NM_001382349.1		c.924C>G	p.Asn308Lys	missense	Exon 9 of 42	NP_001369278.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.852C>G	p.Asn284Lys	missense	Exon 8 of 42	ENSP00000382179.4
MYO5A	ENST00000399231.8	TSL:1	c.852C>G	p.Asn284Lys	missense	Exon 8 of 41	ENSP00000382177.3
MYO5A	ENST00000356338.11	TSL:1	c.852C>G	p.Asn284Lys	missense	Exon 8 of 41	ENSP00000348693.7

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000361

AC:

AN:

248984

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1460704

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33454

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110994

Other (OTH)

AF:

0.0000166

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000256

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.000942

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.21

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

M_CAP

Benign

0.075

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.17

PhyloP100

0.65

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.64

REVEL

Uncertain

0.30

Sift

Benign

0.43

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.17

MutPred

0.57

Gain of methylation at N284 (P = 0.0038)

MVP

0.38

MPC

0.43

ClinPred

0.0077

GERP RS

1.5

Varity_R

0.048

gMVP

0.19

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over