22-25763322-G-C

Position:

• chr22-25763322-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032608.7(MYO18B):​c.131G>C​(p.Gly44Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G44E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16616437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.131G>C	p.Gly44Ala	missense_variant	3/44	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.131G>C	p.Gly44Ala	missense_variant	3/44	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.131G>C	p.Gly44Ala	missense_variant	3/44	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.131G>C	p.Gly44Ala	missense_variant	3/43	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.131G>C		non_coding_transcript_exon_variant	2/42	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.59	.;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.50	N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.046	D;D;D
Vest4		0.37
MutPred		0.21		Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);
MVP		0.76
MPC		0.069
ClinPred		0.39	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs133885; hg19: chr22-26159289;