22-25761101-C-G

Variant names:

• chr22-25761101-C-G
• rs61734946
• NM_032608.7:c.9C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032608.7(MYO18B):​c.9C>G​(p.Ile3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,852 control chromosomes in the GnomAD database, including 26,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1737 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24495 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.175

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016304553).
• BP6: Variant 22-25761101-C-G is Benign according to our data. Variant chr22-25761101-C-G is described in ClinVar as [Benign]. Clinvar id is 1321829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 44	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 44	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 44	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 43	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.9C>G		non_coding_transcript_exon_variant	Exon 1 of 42	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20030 AN: 152148 Hom.: 1737 Cov.: 33

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.142 AC: 35447 AN: 248832 Hom.: 3147 AF XY: 0.147 AC XY: 19781 AN XY: 134990

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.0891

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.000667

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.176 AC: 256892 AN: 1460586 Hom.: 24495 Cov.: 32 AF XY: 0.175 AC XY: 127181 AN XY: 726634

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.0928

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.132 AC: 20025 AN: 152266 Hom.: 1737 Cov.: 33 AF XY: 0.129 AC XY: 9588 AN XY: 74444

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.146

Alfa AF: 0.184 Hom.: 2096

Bravo AF: 0.126

TwinsUK AF: 0.192 AC: 713

ALSPAC AF: 0.178 AC: 687

ESP6500AA AF: 0.0403 AC: 177

ESP6500EA AF: 0.189 AC: 1622

ExAC AF: 0.141 AC: 17150

Asia WGS AF: 0.0430 AC: 152 AN: 3478

EpiCase AF: 0.202

EpiControl AF: 0.204

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T;T;.
Eigen	Benign	0.077
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.77	.;T;T
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M;M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.28
MPC		0.14
ClinPred		0.063	T
GERP RS		-0.90
Varity_R		0.21
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs61734946; hg19: chr22-26157068;