chr2-170382080-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138995.5(MYO3B):​c.1036G>A​(p.Asp346Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MYO3B
NM_138995.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.00

Publications

0 publications found
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)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
MYO3BNM_138995.5 linkc.1036G>A p.Asp346Asn missense_variant Exon 10 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.1036G>A p.Asp346Asn missense_variant Exon 10 of 35 1 NM_138995.5 ENSP00000386213.4 Q8WXR4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 13, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1036G>A (p.D346N) alteration is located in exon 10 (coding exon 10) of the MYO3B gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the aspartic acid (D) at amino acid position 346 to be replaced by an asparagine (N). 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
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.017
.;T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.059
D
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.8
L;L;.
PhyloP100
9.0
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Uncertain
0.33
Sift
Benign
0.083
T;T;T
Sift4G
Benign
0.14
.;.;T
Polyphen
0.59
P;B;.
Vest4
0.71
MutPred
0.65
Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);.;
MVP
0.86
MPC
0.19
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.60
gMVP
0.67
Mutation Taster
=77/23
polymorphism

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

Other links and lift over

hg19: chr2-171238590; API