rs3745349

chr19-17102182-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004145.4(MYO9B):c.465C>T(p.Pro155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,702 control chromosomes in the GnomAD database, including 25,463 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1750 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23713 hom.)
• Consequence: MYO9B NM_004145.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

Genes affected

MYO9B (HGNC:7609): (myosin IXB) This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-2.56 with no splicing effect.
• 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/exons	MANE	UniProt
MYO9B	NM_004145.4	c.465C>T	p.Pro155=	synonymous_variant	2/40	ENST00000682292.1
MYO9B	NM_001130065.2	c.465C>T	p.Pro155=	synonymous_variant	2/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1	c.465C>T	p.Pro155=	synonymous_variant	2/40		NM_004145.4	A2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21112 AN: 152064 Hom.: 1745 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.141 AC: 34997 AN: 248980 Hom.: 2853 AF XY: 0.143 AC XY: 19285 AN XY: 135118

Gnomad AFR exome AF: 0.0557

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0977

Gnomad EAS exome AF: 0.0193

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.174 AC: 254407 AN: 1461520 Hom.: 23713 Cov.: 34 AF XY: 0.173 AC XY: 125550 AN XY: 727050

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0199

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.139 AC: 21136 AN: 152182 Hom.: 1750 Cov.: 32 AF XY: 0.137 AC XY: 10201 AN XY: 74412

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.129

Alfa AF: 0.171 Hom.: 4891

Bravo AF: 0.131

Asia WGS AF: 0.0650 AC: 229 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.2
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3745349; hg19: chr19-17212992; COSMIC: COSV68278094; COSMIC: COSV68278094;