2-170391531-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.1589A>Gā€‹(p.Asn530Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,343,756 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: not found (cov: 31)
Exomes š‘“: 7.4e-7 ( 0 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.72
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, 0.94

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO3BNM_138995.5 linkc.1589A>G p.Asn530Ser missense_variant Exon 15 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.1589A>G p.Asn530Ser missense_variant Exon 15 of 35 1 NM_138995.5 ENSP00000386213.4 Q8WXR4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.44e-7
AC:
1
AN:
1343756
Hom.:
0
Cov.:
23
AF XY:
0.00000149
AC XY:
1
AN XY:
670512
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:
0.0000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1589A>G (p.N530S) alteration is located in exon 15 (coding exon 15) of the MYO3B gene. This alteration results from a A to G substitution at nucleotide position 1589, causing the asparagine (N) at amino acid position 530 to be replaced by a serine (S). 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
0.22
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
.;T;D
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.94
D;D;D
MetaSVM
Uncertain
0.21
D
MutationAssessor
Uncertain
2.2
M;M;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-4.7
D;D;D
REVEL
Pathogenic
0.70
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.013
.;.;D
Polyphen
1.0
D;D;.
Vest4
0.97
MutPred
0.87
Gain of disorder (P = 0.0551);Gain of disorder (P = 0.0551);.;
MVP
0.96
MPC
0.38
ClinPred
1.0
D
GERP RS
6.2
Varity_R
0.86
gMVP
0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-171248041; API