rs133885

chr22-25763322-G-Achr22-25763322-G-C

Variant summary

Our verdict is Benign. Variant got -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. 12/19 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 0.59 (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:3
• Conservation: PhyloP100: 3.88

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]

ACMG classification

Verdict is Benign. Variant got -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 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/exons	MANE	UniProt
MYO18B	NM_032608.7	c.131G>A	p.Gly44Glu	missense_variant	3/44	ENST00000335473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18B	ENST00000335473.12	c.131G>A	p.Gly44Glu	missense_variant	3/44	1	NM_032608.7	A2
MYO18B	ENST00000407587.6	c.131G>A	p.Gly44Glu	missense_variant	3/44	1		P5
MYO18B	ENST00000536101.5	c.131G>A	p.Gly44Glu	missense_variant	3/43	1		A2
MYO18B	ENST00000539302.5	c.131G>A	p.Gly44Glu	missense_variant, NMD_transcript_variant	2/42	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

GnomAD3 exomes AF: 0.549 AC: 135732 AN: 247184 Hom.: 40127 AF XY: 0.535 AC XY: 71840 AN XY: 134212

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 SAS exome AF: 0.546

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

Gnomad4 AFR exome AF: 0.861

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.826

Gnomad4 SAS exome AF: 0.545

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.517

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

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.567

Alfa AF: 0.485 Hom.: 46458

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 17000706) -

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

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
MetaRNN	Benign	5.8e-7	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.1	N;N;N
MutationTaster	Benign	1.0	P;P;P
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

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

LitVar

Other links and lift over

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