dbSNP rs755814896: MYO18B:p.Arg1416Gly (chr22-25877980-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032608.7(MYO18B):c.4246C>G(p.Arg1416Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517

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-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

MYO18B-AS1 links:

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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=0.11553696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.4246C>G	p.Arg1416Gly	missense_variant	Exon 25 of 44	ENST00000335473.12	NP_115997.5	Q8IUG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO18B	ENST00000335473.12 link	c.4246C>G	p.Arg1416Gly	missense_variant	Exon 25 of 44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.4249C>G	p.Arg1417Gly	missense_variant	Exon 25 of 44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.4246C>G	p.Arg1416Gly	missense_variant	Exon 25 of 43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.*1704C>G		non_coding_transcript_exon_variant	Exon 23 of 42	1		ENSP00000437587.1	F5H6I8
MYO18B	ENST00000539302.5 link	n.*1704C>G		3_prime_UTR_variant	Exon 23 of 42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000506

AC:

AN:

197486

Hom.:

AF XY:

0.00000951

AC XY:

AN XY:

105102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000195

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426918

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.0

L;L;.

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.12

Sift

Benign

0.14

T;T;T

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.035

B;B;.

Vest4

0.18

MutPred

0.38

.;.;Loss of MoRF binding (P = 0.0144);

MVP

0.71

MPC

0.12

ClinPred

0.18

GERP RS

0.23

Varity_R

0.14

gMVP

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over