rs9624909

Positions:

• chr22-25826487-C-T

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.2774C>T​(p.Ser925Leu) variant causes a missense change. The variant allele was found at a frequency of 0.212 in 1,612,254 control chromosomes in the GnomAD database, including 38,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (3373 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35295 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.62

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018035173).
• BP6: Variant 22-25826487-C-T is Benign according to our data. Variant chr22-25826487-C-T is described in ClinVar as [Benign]. Clinvar id is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.2774C>T	p.Ser925Leu	missense_variant	14/44	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.2774C>T	p.Ser925Leu	missense_variant	14/44	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.2774C>T	p.Ser925Leu	missense_variant	14/44	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.2774C>T	p.Ser925Leu	missense_variant	14/43	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*232C>T		non_coding_transcript_exon_variant	12/42	1		ENSP00000437587.1
MYO18B	ENST00000539302.5	n.*232C>T		3_prime_UTR_variant	12/42	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31280 AN: 152034 Hom.: 3367 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.184 AC: 45794 AN: 248730 Hom.: 5021 AF XY: 0.184 AC XY: 24861 AN XY: 134886

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.00267

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.213 AC: 310438 AN: 1460100 Hom.: 35295 Cov.: 31 AF XY: 0.210 AC XY: 152738 AN XY: 726354

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.00128

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.206 AC: 31300 AN: 152154 Hom.: 3373 Cov.: 32 AF XY: 0.206 AC XY: 15289 AN XY: 74376

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.207

Alfa AF: 0.217 Hom.: 9176

Bravo AF: 0.202

TwinsUK AF: 0.248 AC: 920

ALSPAC AF: 0.221 AC: 852

ESP6500AA AF: 0.189 AC: 741

ESP6500EA AF: 0.217 AC: 1803

ExAC AF: 0.185 AC: 22314

Asia WGS AF: 0.0610 AC: 212 AN: 3478

EpiCase AF: 0.231

EpiControl AF: 0.228

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	.;D;D
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.3	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.24
MPC		0.36
ClinPred		0.032	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.47

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: rs9624909; hg19: chr22-26222454; COSMIC: COSV59136972;