rs755814896

Variant names:

• chr22-25877980-C-T
• rs755814896
• NM_032608.7:c.4246C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-25877980-C-T
• chr22-25877980-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032608.7(MYO18B):​c.4246C>T​(p.Arg1416Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 1,426,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R1416Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.517
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14506638).

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.4246C>T	p.Arg1416Trp	missense	Exon 25 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.4249C>T	p.Arg1417Trp	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.4246C>T	p.Arg1416Trp	missense	Exon 25 of 44	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4249C>T	p.Arg1417Trp	missense	Exon 25 of 44	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4246C>T	p.Arg1416Trp	missense	Exon 25 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000203 AC: 4 AN: 197486 AF XY: 0.0000190

Gnomad AFR exome AF: 0.0000863

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000705

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000117

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000196 AC: 28 AN: 1426918 Hom.: 0 Cov.: 31 AF XY: 0.0000142 AC XY: 10 AN XY: 706084

African (AFR) AF: 0.0000610 AC: 2 AN: 32774

American (AMR) AF: 0.00 AC: 0 AN: 39540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25414

East Asian (EAS) AF: 0.000237 AC: 9 AN: 38024

South Asian (SAS) AF: 0.0000495 AC: 4 AN: 80846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51322

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

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1094042

Other (OTH) AF: 0.0000169 AC: 1 AN: 59220

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000250 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.52
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.41		Gain of catalytic residue at L1415 (P = 0.0028)
MVP		0.77
MPC		0.067
ClinPred		0.74	D
GERP RS		0.23
Varity_R		0.094
gMVP		0.21
Mutation Taster		=97/3	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: rs755814896; hg19: chr22-26273947; COSMIC: COSV59143695;