rs1016645704

Variant summary

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

The NM_001382347.1(MYO5A):ā€‹c.5612G>Cā€‹(p.Ser1871Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

11
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68
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.5612G>C p.Ser1871Thr 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.5612G>C p.Ser1871Thr missense_variant Exon 42 of 42 5 NM_001382347.1 ENSP00000382179.4 Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249390
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135296
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Aug 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5537G>C (p.S1846T) alteration is located in exon 41 (coding exon 41) of the MYO5A gene. This alteration results from a G to C substitution at nucleotide position 5537, causing the serine (S) at amino acid position 1846 to be replaced by a threonine (T). 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
0.20
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;.;T;T;.;T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;D;D
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.45
T;T;T;T;T;T;T
MetaSVM
Uncertain
0.26
D
MutationAssessor
Uncertain
2.4
M;.;.;.;.;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.6
N;N;.;.;.;N;N
REVEL
Uncertain
0.46
Sift
Benign
0.19
T;T;.;.;.;T;T
Sift4G
Benign
0.20
T;T;T;T;T;T;T
Polyphen
0.80
P;D;.;.;.;.;.
Vest4
0.33
MVP
0.69
MPC
1.9
ClinPred
0.89
D
GERP RS
5.8
Varity_R
0.62
gMVP
0.54

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

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

Other links and lift over

dbSNP: rs1016645704; hg19: chr15-52605924; API