chr22-26027121-C-T

Position:

chr22-26027121-C-T

Variant summary

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

The NM_032608.7(MYO18B):c.7147C>T(p.Arg2383Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,988 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 24 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.625

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=0.008432716).

BP6

Variant 22-26027121-C-T is Benign according to our data. Variant chr22-26027121-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 377088.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00334 (508/152284) while in subpopulation AMR AF= 0.00562 (86/15308). AF 95% confidence interval is 0.00469. There are 2 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7 linkuse as main transcript	c.7147C>T	p.Arg2383Trp	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.7147C>T	p.Arg2383Trp	missense_variant	43/44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 linkuse as main transcript	c.7150C>T	p.Arg2384Trp	missense_variant	43/44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 linkuse as main transcript	c.7147C>T	p.Arg2383Trp	missense_variant	43/43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 linkuse as main transcript	n.*4605C>T		non_coding_transcript_exon_variant	41/42	1		ENSP00000437587.1	F5H6I8
MYO18B	ENST00000539302.5 linkuse as main transcript	n.*4605C>T		3_prime_UTR_variant	41/42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.00334

AC:

508

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00293

AC:

731

AN:

249190

Hom.:

AF XY:

0.00288

AC XY:

389

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00469

Gnomad OTH exome

AF:

0.00512

GnomAD4 exome

AF:

0.00464

AC:

6775

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

3219

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00563

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00334

AC:

508

AN:

152284

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00361

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00151

AC:

ESP6500EA

AF:

0.00493

AC:

ExAC

AF:

0.00302

AC:

365

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00492

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	MYO18B: BP4, BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 08, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

MYO18B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.83

.;T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.17

T;T;T

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.29

B;B;.

Vest4

0.27

MVP

0.80

MPC

0.091

ClinPred

0.017

GERP RS

1.2

Varity_R

0.077

gMVP

0.20

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