rs767265712

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382347.1(MYO5A):​c.5495G>A​(p.Arg1832His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO5ANM_001382347.1 linkc.5495G>A p.Arg1832His missense_variant Exon 42 of 42 ENST00000399233.7 NP_001369276.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO5AENST00000399233.7 linkc.5495G>A p.Arg1832His missense_variant Exon 42 of 42 5 NM_001382347.1 ENSP00000382179.4 Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248852
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135126
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS 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:
0.0000116
AC:
17
AN:
1461678
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000337
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jun 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5420G>A (p.R1807H) alteration is located in exon 41 (coding exon 41) of the MYO5A gene. This alteration results from a G to A substitution at nucleotide position 5420, causing the arginine (R) at amino acid position 1807 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T;.;T;T;.;T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.86
D;D;D;D;D;D;D
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.52
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Benign
1.1
L;.;.;.;.;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.5
N;N;.;.;.;N;N
REVEL
Uncertain
0.48
Sift
Benign
0.055
T;T;.;.;.;T;T
Sift4G
Benign
0.063
T;T;T;T;T;T;T
Polyphen
0.98
D;D;.;.;.;.;.
Vest4
0.46
MVP
0.54
MPC
1.9
ClinPred
0.75
D
GERP RS
5.7
Varity_R
0.46
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs767265712; hg19: chr15-52606041; API