19-17154400-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_004145.4(MYO9B):c.1184C>A(p.Pro395His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,612,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
MYO9B
NM_004145.4 missense
NM_004145.4 missense
Scores
1
8
5
Clinical Significance
Conservation
PhyloP100: 7.48
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MYO9B
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO9B | NM_004145.4 | c.1184C>A | p.Pro395His | missense_variant | 6/40 | ENST00000682292.1 | |
MYO9B | NM_001130065.2 | c.1184C>A | p.Pro395His | missense_variant | 6/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO9B | ENST00000682292.1 | c.1184C>A | p.Pro395His | missense_variant | 6/40 | NM_004145.4 | A2 | ||
ENST00000597216.5 | n.221-1638G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152156Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000804 AC: 20AN: 248654Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 134942
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1459846Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 725960
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2023 | The c.1184C>A (p.P395H) alteration is located in exon 6 (coding exon 5) of the MYO9B gene. This alteration results from a C to A substitution at nucleotide position 1184, causing the proline (P) at amino acid position 395 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D
Vest4
MutPred
Loss of glycosylation at P395 (P = 0.0764);Loss of glycosylation at P395 (P = 0.0764);Loss of glycosylation at P395 (P = 0.0764);Loss of glycosylation at P395 (P = 0.0764);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at