22-25763322-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032608.7(MYO18B):​c.131G>A​(p.Gly44Glu) variant causes a missense change. The variant allele was found at a frequency of 0.492 in 1,612,264 control chromosomes in the GnomAD database, including 206,410 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 28924 hom., cov: 31)
Exomes 𝑓: 0.48 ( 177486 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.88

Publications

52 publications found
Variant links:
Genes affected
MYO18B (HGNC:18150): (myosin XVIIIB) The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jul 2008]
MYO18B Gene-Disease associations (from GenCC):
  • Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=5.7819443E-7).
BP6
Variant 22-25763322-G-A is Benign according to our data. Variant chr22-25763322-G-A is described in CliVar as Benign. Clinvar id is 1245085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25763322-G-A is described in CliVar as Benign. Clinvar id is 1245085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25763322-G-A is described in CliVar as Benign. Clinvar id is 1245085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25763322-G-A is described in CliVar as Benign. Clinvar id is 1245085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25763322-G-A is described in CliVar as Benign. Clinvar id is 1245085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO18BNM_032608.7 linkc.131G>A p.Gly44Glu missense_variant Exon 3 of 44 ENST00000335473.12 NP_115997.5 Q8IUG5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO18BENST00000335473.12 linkc.131G>A p.Gly44Glu missense_variant Exon 3 of 44 1 NM_032608.7 ENSP00000334563.8 Q8IUG5-1
MYO18BENST00000407587.6 linkc.131G>A p.Gly44Glu missense_variant Exon 3 of 44 1 ENSP00000386096.2 Q8IUG5-3
MYO18BENST00000536101.5 linkc.131G>A p.Gly44Glu missense_variant Exon 3 of 43 1 ENSP00000441229.1 Q8IUG5-1
MYO18BENST00000539302.5 linkn.131G>A non_coding_transcript_exon_variant Exon 2 of 42 1 ENSP00000437587.1 F5H6I8

Frequencies

GnomAD3 genomes
AF:
0.590
AC:
89623
AN:
151890
Hom.:
28850
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.842
Gnomad AMI
AF:
0.286
Gnomad AMR
AF:
0.612
Gnomad ASJ
AF:
0.541
Gnomad EAS
AF:
0.825
Gnomad SAS
AF:
0.569
Gnomad FIN
AF:
0.440
Gnomad MID
AF:
0.503
Gnomad NFE
AF:
0.446
Gnomad OTH
AF:
0.566
GnomAD2 exomes
AF:
0.549
AC:
135732
AN:
247184
AF XY:
0.535
show subpopulations
Gnomad AFR exome
AF:
0.852
Gnomad AMR exome
AF:
0.719
Gnomad ASJ exome
AF:
0.537
Gnomad EAS exome
AF:
0.822
Gnomad FIN exome
AF:
0.434
Gnomad NFE exome
AF:
0.439
Gnomad OTH exome
AF:
0.505
GnomAD4 exome
AF:
0.482
AC:
704014
AN:
1460256
Hom.:
177486
Cov.:
47
AF XY:
0.481
AC XY:
349536
AN XY:
726382
show subpopulations
African (AFR)
AF:
0.861
AC:
28756
AN:
33386
American (AMR)
AF:
0.707
AC:
31306
AN:
44268
Ashkenazi Jewish (ASJ)
AF:
0.543
AC:
14160
AN:
26096
East Asian (EAS)
AF:
0.826
AC:
32775
AN:
39682
South Asian (SAS)
AF:
0.545
AC:
46875
AN:
86080
European-Finnish (FIN)
AF:
0.428
AC:
22857
AN:
53362
Middle Eastern (MID)
AF:
0.540
AC:
3097
AN:
5740
European-Non Finnish (NFE)
AF:
0.444
AC:
492997
AN:
1111346
Other (OTH)
AF:
0.517
AC:
31191
AN:
60296
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
18680
37361
56041
74722
93402
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
15294
30588
45882
61176
76470
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.590
AC:
89758
AN:
152008
Hom.:
28924
Cov.:
31
AF XY:
0.592
AC XY:
44015
AN XY:
74292
show subpopulations
African (AFR)
AF:
0.843
AC:
34966
AN:
41500
American (AMR)
AF:
0.612
AC:
9360
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.541
AC:
1878
AN:
3470
East Asian (EAS)
AF:
0.826
AC:
4270
AN:
5170
South Asian (SAS)
AF:
0.570
AC:
2736
AN:
4800
European-Finnish (FIN)
AF:
0.440
AC:
4648
AN:
10552
Middle Eastern (MID)
AF:
0.514
AC:
150
AN:
292
European-Non Finnish (NFE)
AF:
0.446
AC:
30298
AN:
67930
Other (OTH)
AF:
0.567
AC:
1192
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1647
3295
4942
6590
8237
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
722
1444
2166
2888
3610
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.501
Hom.:
94819
Bravo
AF:
0.619
TwinsUK
AF:
0.420
AC:
1559
ALSPAC
AF:
0.431
AC:
1663
ESP6500AA
AF:
0.845
AC:
3219
ESP6500EA
AF:
0.444
AC:
3665
ExAC
AF:
0.543
AC:
65546
Asia WGS
AF:
0.710
AC:
2469
AN:
3478
EpiCase
AF:
0.454
EpiControl
AF:
0.444

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nov 12, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17000706) -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome Benign:1
Sep 05, 2021
Genome-Nilou Lab
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
0.061
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
18
DANN
Benign
0.53
DEOGEN2
Benign
0.011
T;T;.
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.25
.;T;T
MetaRNN
Benign
5.8e-7
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-2.1
N;N;N
PhyloP100
3.9
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
3.3
N;N;N
REVEL
Benign
0.19
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Vest4
0.28
MPC
0.082
ClinPred
0.0014
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.041
gMVP
0.10
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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

dbSNP: rs133885; hg19: chr22-26159289; COSMIC: COSV59127662; API