rs754301736

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138995.5(MYO3B):ā€‹c.394A>Cā€‹(p.Met132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.612
Variant links:
Genes affected
MYO3B (HGNC:15576): (myosin IIIB) This gene encodes one of the class III myosins. Myosins are ATPases, activated by actin, that move along actin filaments in the cell. This class of myosins are characterized by an amino-terminal kinase domain and shown to be present in photoreceptors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042236835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO3BNM_138995.5 linkc.394A>C p.Met132Leu missense_variant Exon 4 of 35 ENST00000408978.9 NP_620482.3 Q8WXR4-1B7ZM71

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO3BENST00000408978.9 linkc.394A>C p.Met132Leu missense_variant Exon 4 of 35 1 NM_138995.5 ENSP00000386213.4 Q8WXR4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249506
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135366
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461846
Hom.:
0
Cov.:
33
AF XY:
0.00000825
AC XY:
6
AN XY:
727228
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
4.0
DANN
Benign
0.65
DEOGEN2
Benign
0.015
.;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0095
N
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.042
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.53
N;N;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.0
N;N;N
REVEL
Benign
0.20
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
.;.;T
Polyphen
0.0
B;B;.
Vest4
0.23
MutPred
0.62
Loss of catalytic residue at M132 (P = 0.0318);Loss of catalytic residue at M132 (P = 0.0318);.;
MVP
0.40
MPC
0.070
ClinPred
0.029
T
GERP RS
-11
Varity_R
0.077
gMVP
0.35

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: rs754301736; hg19: chr2-171070961; API