Variant 2-170217328-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_138995.5(MYO3B):c.536C>G(p.Ala179Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,662 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3B	NM_138995.5 link	c.536C>G	p.Ala179Gly	missense_variant	Exon 6 of 35	ENST00000408978.9	NP_620482.3	Q8WXR4-1B7ZM71

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9 link	c.536C>G	p.Ala179Gly	missense_variant	Exon 6 of 35	1	NM_138995.5	ENSP00000386213.4		Q8WXR4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249558

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135392

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727156

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:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.536C>G (p.A179G) alteration is located in exon 6 (coding exon 6) of the MYO3B gene. This alteration results from a C to G substitution at nucleotide position 536, causing the alanine (A) at amino acid position 179 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

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.014

.;.;D

Polyphen

1.0

D;D;.

Vest4

0.64

MutPred

0.68

Gain of disorder (P = 0.0684);Gain of disorder (P = 0.0684);.;

MVP

0.85

MPC

0.20

ClinPred

0.73

GERP RS

6.1

Varity_R

0.49

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over