chr19-17102323-G-A

Position:

• chr19-17102323-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004145.4(MYO9B):​c.606G>A​(p.Met202Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO9B NM_004145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

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]

MYO9B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.606G>A	p.Met202Ile	missense_variant	2/40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.606G>A	p.Met202Ile	missense_variant	2/40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.606G>A	p.Met202Ile	missense_variant	2/40		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.606G>A (p.M202I) alteration is located in exon 2 (coding exon 1) of the MYO9B gene. This alteration results from a G to A substitution at nucleotide position 606, causing the methionine (M) at amino acid position 202 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	.;D;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.8	L;.;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.0	.;.;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0090	.;.;D;.
Sift4G	Uncertain	0.011	D;D;D;D
Vest4		0.32
MutPred		0.54		Gain of catalytic residue at M202 (P = 0.0324);Gain of catalytic residue at M202 (P = 0.0324);Gain of catalytic residue at M202 (P = 0.0324);Gain of catalytic residue at M202 (P = 0.0324);
MVP		0.64
MPC		1.2
ClinPred		0.86	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17213133;