chr19-17195222-T-C

Variant names:

• chr19-17195222-T-C
• rs2279003
• NM_004145.4:c.3795T>C

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.3795T>C​(p.Pro1265Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,611,194 control chromosomes in the GnomAD database, including 310,770 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 0.70 (38941 hom., cov: 28)
  • Exomes 𝑓: 0.61 (271829 hom.)
• Consequence: MYO9B NM_004145.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• 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=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.035 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	NM_004145.4	MANE Select	c.3795T>C	p.Pro1265Pro	synonymous	Exon 22 of 40	NP_004136.2
	MYO9B	NM_001130065.2		c.3795T>C	p.Pro1265Pro	synonymous	Exon 22 of 40	NP_001123537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	ENST00000682292.1	MANE Select	c.3795T>C	p.Pro1265Pro	synonymous	Exon 22 of 40	ENSP00000507803.1
	MYO9B	ENST00000595618.5	TSL:1	c.3795T>C	p.Pro1265Pro	synonymous	Exon 22 of 40	ENSP00000471457.1
	MYO9B	ENST00000594824.5	TSL:5	c.3795T>C	p.Pro1265Pro	synonymous	Exon 22 of 40	ENSP00000471367.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106221 AN: 151496 Hom.: 38885 Cov.: 28

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.603

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.655 AC: 158220 AN: 241726 AF XY: 0.642

Gnomad AFR exome AF: 0.929

Gnomad AMR exome AF: 0.805

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.774

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.606 AC: 883996 AN: 1459580 Hom.: 271829 Cov.: 86 AF XY: 0.605 AC XY: 439290 AN XY: 726102

African (AFR) AF: 0.935 AC: 31302 AN: 33470

American (AMR) AF: 0.799 AC: 35670 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 12531 AN: 26092

East Asian (EAS) AF: 0.753 AC: 29866 AN: 39678

South Asian (SAS) AF: 0.638 AC: 54976 AN: 86230

European-Finnish (FIN) AF: 0.605 AC: 31398 AN: 51916

Middle Eastern (MID) AF: 0.632 AC: 3644 AN: 5768

European-Non Finnish (NFE) AF: 0.582 AC: 647378 AN: 1111480

Other (OTH) AF: 0.617 AC: 37231 AN: 60328

GnomAD4 genome AF: 0.701 AC: 106331 AN: 151614 Hom.: 38941 Cov.: 28 AF XY: 0.702 AC XY: 51954 AN XY: 74040

African (AFR) AF: 0.921 AC: 38106 AN: 41386

American (AMR) AF: 0.737 AC: 11243 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1691 AN: 3462

East Asian (EAS) AF: 0.762 AC: 3869 AN: 5076

South Asian (SAS) AF: 0.657 AC: 3136 AN: 4774

European-Finnish (FIN) AF: 0.615 AC: 6497 AN: 10556

Middle Eastern (MID) AF: 0.607 AC: 176 AN: 290

European-Non Finnish (NFE) AF: 0.585 AC: 39673 AN: 67810

Other (OTH) AF: 0.683 AC: 1436 AN: 2104

Alfa AF: 0.619 Hom.: 16642

Bravo AF: 0.724

Asia WGS AF: 0.695 AC: 2413 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.18
PhyloP100		-0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs2279003; hg19: chr19-17306031; COSMIC: COSV68277217; COSMIC: COSV68277217;