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GeneBe

19-17101802-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_004145.4(MYO9B):c.85G>A(p.Glu29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,606,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
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=0.18075866).
BS2
High AC in GnomAdExome at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYO9BNM_004145.4 linkuse as main transcriptc.85G>A p.Glu29Lys missense_variant 2/40 ENST00000682292.1
MYO9BNM_001130065.2 linkuse as main transcriptc.85G>A p.Glu29Lys missense_variant 2/40

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYO9BENST00000682292.1 linkuse as main transcriptc.85G>A p.Glu29Lys missense_variant 2/40 NM_004145.4 A2Q13459-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000292
AC:
7
AN:
239544
Hom.:
0
AF XY:
0.0000230
AC XY:
3
AN XY:
130676
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000167
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000182
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000275
AC:
40
AN:
1453858
Hom.:
0
Cov.:
31
AF XY:
0.0000332
AC XY:
24
AN XY:
723150
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsJun 30, 2023The c.85G>A (p.E29K) 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 85, causing the glutamic acid (E) at amino acid position 29 to be replaced by a lysine (K). 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
0.077
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.48
Cadd
Benign
21
Dann
Uncertain
1.0
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.35
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.;L;.
MutationTaster
Benign
0.85
N
PrimateAI
Benign
0.47
T
Sift4G
Uncertain
0.056
T;T;T;T
Vest4
0.38
MutPred
0.45
Gain of ubiquitination at E29 (P = 0.0117);Gain of ubiquitination at E29 (P = 0.0117);Gain of ubiquitination at E29 (P = 0.0117);Gain of ubiquitination at E29 (P = 0.0117);
MVP
0.38
MPC
1.1
ClinPred
0.11
T
GERP RS
2.7
gMVP
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770104097; hg19: chr19-17212612; API