22-25878008-G-A

Position:

chr22-25878008-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032608.7(MYO18B):c.4274G>A(p.Arg1425Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000423 in 1,584,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 6.82

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1287831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7 linkuse as main transcript	c.4274G>A	p.Arg1425Gln	missense_variant	25/44	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.4274G>A	p.Arg1425Gln	missense_variant	25/44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 linkuse as main transcript	c.4277G>A	p.Arg1426Gln	missense_variant	25/44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 linkuse as main transcript	c.4274G>A	p.Arg1425Gln	missense_variant	25/43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 linkuse as main transcript	n.*1732G>A		non_coding_transcript_exon_variant	23/42	1		ENSP00000437587.1	F5H6I8
MYO18B	ENST00000539302.5 linkuse as main transcript	n.*1732G>A		3_prime_UTR_variant	23/42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000730

AC:

AN:

205554

Hom.:

AF XY:

0.0000820

AC XY:

AN XY:

109814

show subpopulations

Gnomad AFR exome

AF:

0.000412

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000404

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1432852

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

709692

show subpopulations

Gnomad4 AFR exome

AF:

0.000213

Gnomad4 AMR exome

AF:

0.0000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000235

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000228

Gnomad4 OTH exome

AF:

0.0000673

GnomAD4 genome

AF:

0.000131

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MYO18B-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2024

The MYO18B c.4274G>A variant is predicted to result in the amino acid substitution p.Arg1425Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.043% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2022

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1425 of the MYO18B protein (p.Arg1425Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYO18B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1481475). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.52

D;D;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.3

M;M;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.46

Sift

Benign

0.062

T;T;T

Sift4G

Uncertain

0.047

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.22

MVP

0.96

MPC

0.42

ClinPred

0.86

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.43

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