2-170369229-A-G

Variant summary

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

The NM_138995.5(MYO3B):ā€‹c.823A>Gā€‹(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 (ā˜…ā˜…). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: š‘“ 0.010 ( 21 hom., cov: 33)
Exomes š‘“: 0.0011 ( 30 hom. )

Consequence

MYO3B
NM_138995.5 missense

Scores

1
3
14

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

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 rank MANE Protein UniProt
MYO3BNM_138995.5 linkc.823A>G p.Ile275Val missense_variant Exon 9 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.823A>G p.Ile275Val missense_variant Exon 9 of 35 1 NM_138995.5 ENSP00000386213.4 Q8WXR4-1

Frequencies

GnomAD3 genomes
AF:
0.00996
AC:
1515
AN:
152124
Hom.:
21
Cov.:
33
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.:
4
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.:
30
Cov.:
30
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.:
21
Cov.:
33
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.:
8
Bravo
AF:
0.0114
ESP6500AA
AF:
0.0362
AC:
133
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00286
AC:
346
Asia WGS
AF:
0.00144
AC:
5
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Feb 20, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Benign
0.72
DEOGEN2
Benign
0.015
.;T;T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.66
T;T;T
MetaRNN
Benign
0.0084
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
N;N;.
PrimateAI
Uncertain
0.56
T
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
T
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.

Other links and lift over

dbSNP: rs10209102; hg19: chr2-171225739; API