22-25878007-C-G

Variant names:

• chr22-25878007-C-G
• rs376264620
• NM_032608.7:c.4273C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032608.7(MYO18B):​c.4273C>G​(p.Arg1425Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R1425W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36552188).

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.4273C>G	p.Arg1425Gly	missense	Exon 25 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.4276C>G	p.Arg1426Gly	missense	Exon 25 of 44	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.4273C>G	p.Arg1425Gly	missense	Exon 25 of 44	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4276C>G	p.Arg1426Gly	missense	Exon 25 of 44	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4273C>G	p.Arg1425Gly	missense	Exon 25 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432442 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 709478

African (AFR) AF: 0.00 AC: 0 AN: 32880

American (AMR) AF: 0.00 AC: 0 AN: 40630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25508

East Asian (EAS) AF: 0.00 AC: 0 AN: 38352

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097024

Other (OTH) AF: 0.00 AC: 0 AN: 59422

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	0.017
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.37	T
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		0.45
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.35		Gain of ubiquitination at K1424 (P = 0.027)
MVP		0.92
MPC		0.44
ClinPred		0.97	D
GERP RS		1.8
Varity_R		0.32
gMVP		0.57
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs376264620; hg19: chr22-26273974;