19-17102231-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_004145.4(MYO9B):c.514C>G(p.Gln172Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYO9B NM_004145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, MYO9B
• BP4: Computational evidence support a benign effect (MetaRNN=0.22222921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9B	NM_004145.4	c.514C>G	p.Gln172Glu	missense_variant	2/40	ENST00000682292.1
MYO9B	NM_001130065.2	c.514C>G	p.Gln172Glu	missense_variant	2/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1	c.514C>G	p.Gln172Glu	missense_variant	2/40		NM_004145.4	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Nov 17, 2023

The c.514C>G (p.Q172E) alteration is located in exon 2 (coding exon 1) of the MYO9B gene. This alteration results from a C to G substitution at nucleotide position 514, causing the glutamine (Q) at amino acid position 172 to be replaced by a glutamic acid (E). 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	Benign	0.12
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Benign	0.029
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	0.56	N;.;N;.
MutationTaster	Benign	0.60	N
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.11	T;T;T;T
Vest4		0.28
MutPred		0.39		Loss of MoRF binding (P = 0.0503);Loss of MoRF binding (P = 0.0503);Loss of MoRF binding (P = 0.0503);Loss of MoRF binding (P = 0.0503);
MVP		0.68
MPC		1.2
ClinPred		0.40	T
GERP RS		5.6
gMVP		0.79

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: chr19-17213041;