Genetic Variant NM_032608.7:c.4246C>G (chr22-25877980-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1416W) has been classified as Uncertain significance.

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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11553696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.4246C>G	p.Arg1416Gly	missense	Exon 25 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.4249C>G	p.Arg1417Gly	missense	Exon 25 of 44	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.4246C>G	p.Arg1416Gly	missense	Exon 25 of 44	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6	TSL:1	c.4249C>G	p.Arg1417Gly	missense	Exon 25 of 44	ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5	TSL:1	c.4246C>G	p.Arg1416Gly	missense	Exon 25 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000506

AC:

AN:

197486

AF XY:

0.00000951

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 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

African (AFR)

AF:

0.00

AC:

AN:

32774

American (AMR)

AF:

0.00

AC:

AN:

39540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25414

East Asian (EAS)

AF:

0.00

AC:

AN:

38024

South Asian (SAS)

AF:

0.00

AC:

AN:

80846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1094042

Other (OTH)

AF:

0.00

AC:

AN:

59220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.10

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.81

M_CAP

Benign

0.036

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.0

PhyloP100

0.52

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.12

Sift

Benign

0.14

Sift4G

Uncertain

0.037

Polyphen

0.035

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

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over