22-25877998-G-C

Variant names:

• chr22-25877998-G-C
• rs2091247378
• NM_032608.7:c.4264G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032608.7(MYO18B):​c.4264G>C​(p.Glu1422Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3121153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4264G>C	p.Glu1422Gln	missense_variant	Exon 25 of 44	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.4264G>C	p.Glu1422Gln	missense_variant	Exon 25 of 44	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.4267G>C	p.Glu1423Gln	missense_variant	Exon 25 of 44	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.4264G>C	p.Glu1422Gln	missense_variant	Exon 25 of 43	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*1722G>C		non_coding_transcript_exon_variant	Exon 23 of 42	1		ENSP00000437587.1
MYO18B	ENST00000539302.5	n.*1722G>C		3_prime_UTR_variant	Exon 23 of 42	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 02, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1422 of the MYO18B protein (p.Glu1422Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYO18B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.076	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.32
MutPred		0.29		.;.;Gain of MoRF binding (P = 0.0306);
MVP		0.95
MPC		0.39
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.37

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

Other links and lift over

dbSNP: rs2091247378; hg19: chr22-26273965;