Variant 22-25761101-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032608.7(MYO18B):c.9C>G(p.Ile3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,852 control chromosomes in the GnomAD database, including 26,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1737 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24495 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.175

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 links:

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=0.0016304553).

BP6

Variant 22-25761101-C-G is Benign according to our data. Variant chr22-25761101-C-G is described in ClinVar as [Benign]. Clinvar id is 1321829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18B	NM_032608.7 linkuse as main transcript	c.9C>G	p.Ile3Met	missense_variant	2/44	ENST00000335473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18B	ENST00000335473.12 linkuse as main transcript	c.9C>G	p.Ile3Met	missense_variant	2/44	1	NM_032608.7	A2	Q8IUG5-1
MYO18B	ENST00000407587.6 linkuse as main transcript	c.9C>G	p.Ile3Met	missense_variant	2/44	1		P5	Q8IUG5-3
MYO18B	ENST00000536101.5 linkuse as main transcript	c.9C>G	p.Ile3Met	missense_variant	2/43	1		A2	Q8IUG5-1
MYO18B	ENST00000539302.5 linkuse as main transcript	c.9C>G	p.Ile3Met	missense_variant, NMD_transcript_variant	1/42	1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20030

AN:

152148

Hom.:

1737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.142

AC:

35447

AN:

248832

Hom.:

3147

AF XY:

0.147

AC XY:

19781

AN XY:

134990

show subpopulations

Gnomad AFR exome

AF:

0.0352

Gnomad AMR exome

AF:

0.0891

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.000667

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.176

AC:

256892

AN:

1460586

Hom.:

24495

Cov.:

AF XY:

0.175

AC XY:

127181

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.0343

Gnomad4 AMR exome

AF:

0.0928

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.132

AC:

20025

AN:

152266

Hom.:

1737

Cov.:

AF XY:

0.129

AC XY:

9588

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0393

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.184

Hom.:

2096

Bravo

AF:

0.126

TwinsUK

AF:

0.192

AC:

713

ALSPAC

AF:

0.178

AC:

687

ESP6500AA

AF:

0.0403

AC:

177

ESP6500EA

AF:

0.189

AC:

1622

ExAC

AF:

0.141

AC:

17150

Asia WGS

AF:

0.0430

AC:

152

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;T;.

Eigen

Benign

0.077

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.56

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

0.98

P;P;P

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.28

MPC

0.14

ClinPred

0.063

GERP RS

-0.90

Varity_R

0.21

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over