chr19-17102321-A-T

Position:

• chr19-17102321-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004145.4(MYO9B):​c.604A>T​(p.Met202Leu) 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. 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: 2.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20926479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.604A>T	p.Met202Leu	missense_variant	2/40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.604A>T	p.Met202Leu	missense_variant	2/40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.604A>T	p.Met202Leu	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

Dec 04, 2024

The c.604A>T (p.M202L) alteration is located in exon 2 (coding exon 1) of the MYO9B gene. This alteration results from a A to T substitution at nucleotide position 604, causing the methionine (M) at amino acid position 202 to be replaced by a leucine (L). 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	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.27	.;T;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	.;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.93	L;.;L;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.8	.;.;N;.
REVEL	Benign	0.19
Sift	Benign	0.59	.;.;T;.
Sift4G	Benign	0.47	T;T;T;T
Vest4		0.30
MutPred		0.48		Loss of methylation at K198 (P = 0.069);Loss of methylation at K198 (P = 0.069);Loss of methylation at K198 (P = 0.069);Loss of methylation at K198 (P = 0.069);
MVP		0.44
MPC		0.69
ClinPred		0.068	T
GERP RS		0.76
gMVP		0.72

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: chr19-17213131;