19-17102182-C-T

Variant names:

• chr19-17102182-C-T
• rs3745349
• NM_004145.4:c.465C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004145.4(MYO9B):​c.465C>T​(p.Pro155Pro) 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.465C>T	p.Pro155Pro	synonymous_variant	Exon 2 of 40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.465C>T	p.Pro155Pro	synonymous_variant	Exon 2 of 40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.465C>T	p.Pro155Pro	synonymous_variant	Exon 2 of 40		NM_004145.4	ENSP00000507803.1

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

GnomAD2 exomes AF: 0.141 AC: 34997 AN: 248980 AF XY: 0.143

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 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

African (AFR) AF: 0.0531 AC: 1777 AN: 33480

American (AMR) AF: 0.122 AC: 5463 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2796 AN: 26136

East Asian (EAS) AF: 0.0199 AC: 790 AN: 39700

South Asian (SAS) AF: 0.116 AC: 9997 AN: 86256

European-Finnish (FIN) AF: 0.162 AC: 8609 AN: 53254

Middle Eastern (MID) AF: 0.105 AC: 608 AN: 5768

European-Non Finnish (NFE) AF: 0.193 AC: 215115 AN: 1111832

Other (OTH) AF: 0.153 AC: 9252 AN: 60370

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

African (AFR) AF: 0.0604 AC: 2510 AN: 41550

American (AMR) AF: 0.139 AC: 2118 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3466

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5170

South Asian (SAS) AF: 0.108 AC: 523 AN: 4824

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13245 AN: 67970

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.168 Hom.: 10023

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
PhyloP100		-2.6
PromoterAI		0.0013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=83/17	polymorphism (auto)

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