chr22-25878007-C-T

Variant names:

• chr22-25878007-C-T
• rs376264620
• NM_032608.7:c.4273C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032608.7(MYO18B):​c.4273C>T​(p.Arg1425Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,584,572 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1425Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.445
• Publications: 1 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-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20426586).

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.4273C>T	p.Arg1425Trp	missense	Exon 25 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.4276C>T	p.Arg1426Trp	missense	Exon 25 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.4273C>T	p.Arg1425Trp	missense	Exon 25 of 44	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4276C>T	p.Arg1426Trp	missense	Exon 25 of 44	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4273C>T	p.Arg1425Trp	missense	Exon 25 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000293 AC: 6 AN: 204942 AF XY: 0.0000183

Gnomad AFR exome AF: 0.0000830

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000521

Gnomad NFE exome AF: 0.0000335

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 51 AN: 1432440 Hom.: 0 Cov.: 31 AF XY: 0.0000395 AC XY: 28 AN XY: 709476

African (AFR) AF: 0.0000912 AC: 3 AN: 32880

American (AMR) AF: 0.0000246 AC: 1 AN: 40630

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25508

East Asian (EAS) AF: 0.000183 AC: 7 AN: 38352

South Asian (SAS) AF: 0.00 AC: 0 AN: 81292

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000310 AC: 34 AN: 1097022

Other (OTH) AF: 0.0000673 AC: 4 AN: 59422

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152132 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74332

African (AFR) AF: 0.000169 AC: 7 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000788 Hom.: 0

Bravo AF: 0.000147

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000665 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	0.025
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.085	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.20	T
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		0.45
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.35
MVP		0.94
MPC		0.40
ClinPred		0.98	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.56
Mutation Taster		=92/8	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: rs376264620; hg19: chr22-26273974;