2-170369256-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138995.5(MYO3B):​c.850G>A​(p.Val284Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000626 in 1,613,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91
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]
MYO3B-AS1 (HGNC:40713): (MYO3B antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22993481).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO3BNM_138995.5 linkc.850G>A p.Val284Ile missense_variant Exon 9 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.850G>A p.Val284Ile missense_variant Exon 9 of 35 1 NM_138995.5 ENSP00000386213.4 Q8WXR4-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD3 exomes
AF:
0.0000442
AC:
11
AN:
248996
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135086
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000684
AC:
100
AN:
1461086
Hom.:
0
Cov.:
30
AF XY:
0.0000674
AC XY:
49
AN XY:
726818
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000929
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000756
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000903
Hom.:
0
ExAC
AF:
0.0000414
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.850G>A (p.V284I) alteration is located in exon 9 (coding exon 9) of the MYO3B gene. This alteration results from a G to A substitution at nucleotide position 850, causing the valine (V) at amino acid position 284 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
.;T;T
Eigen
Benign
-0.047
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.080
N;N;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.88
N;N;N
REVEL
Benign
0.065
Sift
Benign
0.11
T;T;T
Sift4G
Benign
0.17
.;.;T
Polyphen
0.046
B;B;.
Vest4
0.17
MutPred
0.52
Gain of catalytic residue at V284 (P = 0.172);Gain of catalytic residue at V284 (P = 0.172);.;
MVP
0.59
MPC
0.071
ClinPred
0.094
T
GERP RS
5.2
Varity_R
0.20
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs759681607; hg19: chr2-171225766; COSMIC: COSV58692949; API