Variant 2-170217346-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138995.5(MYO3B):c.554G>A(p.Arg185His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,614,032 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 34 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00914228).

BP6

Variant 2-170217346-G-A is Benign according to our data. Variant chr2-170217346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651532.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3B	NM_138995.5 linkuse as main transcript	c.554G>A	p.Arg185His	missense_variant	6/35	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9 linkuse as main transcript	c.554G>A	p.Arg185His	missense_variant	6/35	1	NM_138995.5	ENSP00000386213	P1	Q8WXR4-1

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

726

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00614

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00517

AC:

1289

AN:

249562

Hom.:

AF XY:

0.00526

AC XY:

712

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000946

Gnomad SAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.00576

Gnomad OTH exome

AF:

0.00478

GnomAD4 exome

AF:

0.00553

AC:

8085

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

4020

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00431

Gnomad4 SAS exome

AF:

0.00301

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.00577

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.00476

AC:

725

AN:

152282

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

401

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0196

Gnomad4 NFE

AF:

0.00613

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00504

Hom.:

Bravo

AF:

0.00331

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000523

AC:

ESP6500EA

AF:

0.00582

AC:

ExAC

AF:

0.00489

AC:

591

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MYO3B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Benign

0.88

DEOGEN2

Benign

0.022

.;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.0091

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Uncertain

0.29

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.11

.;.;T

Polyphen

0.69

P;P;.

Vest4

0.63

MVP

0.87

MPC

0.16

ClinPred

0.048

GERP RS

6.1

Varity_R

0.39

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

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