2-170386229-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_138995.5(MYO3B):ā€‹c.1331A>Gā€‹(p.Glu444Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

12
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO3BNM_138995.5 linkc.1331A>G p.Glu444Gly missense_variant Exon 13 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.1331A>G p.Glu444Gly missense_variant Exon 13 of 35 1 NM_138995.5 ENSP00000386213.4 Q8WXR4-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
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
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461342
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726976
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.000169
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1331A>G (p.E444G) alteration is located in exon 13 (coding exon 13) of the MYO3B gene. This alteration results from a A to G substitution at nucleotide position 1331, causing the glutamic acid (E) at amino acid position 444 to be replaced by a glycine (G). 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
Uncertain
0.43
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.42
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.56
.;D;D
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.95
D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.2
H;H;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-6.1
D;D;D
REVEL
Pathogenic
0.93
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.0040
.;.;D
Polyphen
1.0
D;D;.
Vest4
0.79
MVP
0.99
MPC
0.46
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.85
gMVP
0.86

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: rs1005812892; hg19: chr2-171242739; API