chr22-25761114-G-A

Variant names:

• chr22-25761114-G-A
• rs139296373
• NM_032608.7:c.22G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_032608.7(MYO18B):​c.22G>A​(p.Ala8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000213 in 1,613,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A8A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 5.75
• Publications: 8 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 Gene-Disease associations (from GenCC):

• Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31344587).

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.22G>A	p.Ala8Thr	missense	Exon 2 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.22G>A	p.Ala8Thr	missense	Exon 2 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.22G>A	p.Ala8Thr	missense	Exon 2 of 44	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.22G>A	p.Ala8Thr	missense	Exon 2 of 44	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.22G>A	p.Ala8Thr	missense	Exon 2 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152142 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000213 AC: 53 AN: 248816 AF XY: 0.000259

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.0000952

Gnomad NFE exome AF: 0.000389

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000216 AC: 315 AN: 1461138 Hom.: 0 Cov.: 32 AF XY: 0.000217 AC XY: 158 AN XY: 726902

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.000246 AC: 13 AN: 52848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000255 AC: 283 AN: 1111860

Other (OTH) AF: 0.000149 AC: 9 AN: 60372

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74446

African (AFR) AF: 0.0000481 AC: 2 AN: 41550

American (AMR) AF: 0.000523 AC: 8 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68018

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000274 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000234 AC: 2

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000273

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.048	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.31	T
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.54
MVP		0.91
MPC		0.36
ClinPred		0.17	T
GERP RS		5.3
Varity_R		0.17
gMVP		0.43
Mutation Taster		=71/29	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: rs139296373; hg19: chr22-26157081; COSMIC: COSV59124452; COSMIC: COSV59124452;