chr19-17154328-T-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_004145.4(MYO9B):āc.1112T>Cā(p.Ile371Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,612,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 31)
Exomes š: 0.000013 ( 0 hom. )
Consequence
MYO9B
NM_004145.4 missense
NM_004145.4 missense
Scores
3
11
Clinical Significance
Conservation
PhyloP100: 4.55
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 -5 ACMG points.
PP2
Missense variant where missense usually causes diseases, MYO9B
BP4
Computational evidence support a benign effect (MetaRNN=0.0803453).
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO9B | NM_004145.4 | c.1112T>C | p.Ile371Thr | missense_variant | 6/40 | ENST00000682292.1 | |
MYO9B | NM_001130065.2 | c.1112T>C | p.Ile371Thr | missense_variant | 6/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO9B | ENST00000682292.1 | c.1112T>C | p.Ile371Thr | missense_variant | 6/40 | NM_004145.4 | A2 | ||
ENST00000597216.5 | n.221-1566A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152100Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248810Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135012
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459956Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 725954
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74418
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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 | Aug 17, 2021 | The c.1112T>C (p.I371T) alteration is located in exon 6 (coding exon 5) of the MYO9B gene. This alteration results from a T to C substitution at nucleotide position 1112, causing the isoleucine (I) at amino acid position 371 to be replaced by a threonine (T). 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
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T
Vest4
MutPred
Gain of disorder (P = 0.0191);Gain of disorder (P = 0.0191);Gain of disorder (P = 0.0191);Gain of disorder (P = 0.0191);
MVP
MPC
ClinPred
T
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