22-25874392-G-C

Variant names:

• chr22-25874392-G-C
• NM_032608.7:c.4058G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032608.7(MYO18B):​c.4058G>C​(p.Arg1353Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4058G>C	p.Arg1353Pro	missense_variant	Exon 23 of 44	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.4058G>C	p.Arg1353Pro	missense_variant	Exon 23 of 44	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.4061G>C	p.Arg1354Pro	missense_variant	Exon 23 of 44	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.4058G>C	p.Arg1353Pro	missense_variant	Exon 23 of 43	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*1516G>C		non_coding_transcript_exon_variant	Exon 21 of 42	1		ENSP00000437587.1
MYO18B	ENST00000539302.5	n.*1516G>C		3_prime_UTR_variant	Exon 21 of 42	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727052

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;D;.
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Pathogenic	3.0	M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.8	D;D;D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.91
MutPred		0.73		.;.;Loss of MoRF binding (P = 0.001);
MVP		0.97
MPC		0.47
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-26270359;