chr22-25763322-G-A

Variant names:

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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G44V) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.48 ( 177486 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

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

MYO18B links:

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 ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.131G>A	p.Gly44Glu	missense	Exon 3 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.131G>A	p.Gly44Glu	missense	Exon 3 of 44	NP_001305174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.131G>A	p.Gly44Glu	missense	Exon 3 of 44	ENSP00000334563.8
MYO18B	ENST00000407587.6	TSL:1	c.131G>A	p.Gly44Glu	missense	Exon 3 of 44	ENSP00000386096.2
MYO18B	ENST00000536101.5	TSL:1	c.131G>A	p.Gly44Glu	missense	Exon 3 of 43	ENSP00000441229.1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89623

AN:

151890

Hom.:

28850

Cov.:

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.:

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

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

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.:

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

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

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.011

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.25

MetaRNN

Benign

5.8e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.1

PhyloP100

3.9

PrimateAI

Uncertain

0.63

PROVEAN

Benign

3.3

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.28

MPC

0.082

ClinPred

0.0014

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over