22-25763322-G-A

Variant names:

• chr22-25763322-G-A
• rs133885
• NM_032608.7:c.131G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.88
• Publications: 52 publications found

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

ACMG classification

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
MYO18B	NM_032608.7	c.131G>A	p.Gly44Glu	missense_variant	Exon 3 of 44	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.131G>A	p.Gly44Glu	missense_variant	Exon 3 of 44	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.131G>A	p.Gly44Glu	missense_variant	Exon 3 of 44	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.131G>A	p.Gly44Glu	missense_variant	Exon 3 of 43	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.131G>A		non_coding_transcript_exon_variant	Exon 2 of 42	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89623 AN: 151890 Hom.: 28850 Cov.: 31

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

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

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

GnomAD4 genome AF: 0.590 AC: 89758 AN: 152008 Hom.: 28924 Cov.: 31 AF XY: 0.592 AC XY: 44015 AN XY: 74292

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

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

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

Other links and lift over

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