Variant chr2-170369229-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138995.5(MYO3B):c.823A>G(p.Ile275Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,612,852 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.010 ( 21 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 30 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.25

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:

MYO3B-AS1 (HGNC:40713): (MYO3B antisense RNA 1)

MYO3B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008387089).

BP6

Variant 2-170369229-A-G is Benign according to our data. Variant chr2-170369229-A-G is described in ClinVar as [Benign]. Clinvar id is 786868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00997 (1518/152242) while in subpopulation AFR AF= 0.0351 (1458/41540). AF 95% confidence interval is 0.0336. There are 21 homozygotes in gnomad4. There are 693 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3B	NM_138995.5 linkuse as main transcript	c.823A>G	p.Ile275Val	missense_variant	9/35	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.823A>G	p.Ile275Val	missense_variant	9/35	1	NM_138995.5	ENSP00000386213	P1	Q8WXR4-1
MYO3B-AS1	ENST00000625968.2 linkuse as main transcript	n.196+14598T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00996

AC:

1515

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00238

AC:

593

AN:

248922

Hom.:

AF XY:

0.00167

AC XY:

225

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.0343

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.00111

AC:

1619

AN:

1460610

Hom.:

Cov.:

AF XY:

0.000907

AC XY:

659

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.0407

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00997

AC:

1518

AN:

152242

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0351

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00620

Hom.:

Bravo

AF:

0.0114

ESP6500AA

AF:

0.0362

AC:

133

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00286

AC:

346

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.015

.;T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;N;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.15

N;N;N

REVEL

Benign

0.18

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.87

.;.;T

Polyphen

0.14

B;B;.

Vest4

0.52

MVP

0.73

MPC

0.070

ClinPred

0.053

GERP RS

6.1

Varity_R

0.14

gMVP

0.41

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