22-26027319-C-T

Position:

chr22-26027319-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_032608.7(MYO18B):c.7345C>T(p.Arg2449Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,613,998 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 33 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.880

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:

MYO18B (HGNC:):

MYO18B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023308277).

BP6

Variant 22-26027319-C-T is Benign according to our data. Variant chr22-26027319-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 587478.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00445 (678/152306) while in subpopulation NFE AF= 0.00691 (470/68022). AF 95% confidence interval is 0.00639. There are 3 homozygotes in gnomad4. There are 295 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7 linkuse as main transcript	c.7345C>T	p.Arg2449Trp	missense_variant	43/44	ENST00000335473.12	NP_115997.5	Q8IUG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO18B	ENST00000335473.12 linkuse as main transcript	c.7345C>T	p.Arg2449Trp	missense_variant	43/44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 linkuse as main transcript	c.7348C>T	p.Arg2450Trp	missense_variant	43/44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 linkuse as main transcript	c.7345C>T	p.Arg2449Trp	missense_variant	43/43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 linkuse as main transcript	n.*4803C>T		non_coding_transcript_exon_variant	41/42	1		ENSP00000437587.1	F5H6I8
MYO18B	ENST00000539302.5 linkuse as main transcript	n.*4803C>T		3_prime_UTR_variant	41/42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.00446

AC:

678

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00691

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00459

AC:

1144

AN:

249218

Hom.:

AF XY:

0.00475

AC XY:

642

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00330

Gnomad FIN exome

AF:

0.00316

Gnomad NFE exome

AF:

0.00681

Gnomad OTH exome

AF:

0.00612

GnomAD4 exome

AF:

0.00573

AC:

8373

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00571

AC XY:

4151

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00440

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00354

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.00654

Gnomad4 OTH exome

AF:

0.00522

GnomAD4 genome

AF:

0.00445

AC:

678

AN:

152306

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00691

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00636

Hom.:

Bravo

AF:

0.00436

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000998

AC:

ESP6500EA

AF:

0.00577

AC:

ExAC

AF:

0.00485

AC:

586

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00628

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	MYO18B: BS2 -

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

T;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Pathogenic

0.80

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.6

D;D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.70

MVP

0.93

MPC

0.40

ClinPred

0.036

GERP RS

2.9

Varity_R

0.47

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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