19-17195222-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004145.4(MYO9B):​c.3795T>C​(p.Pro1265Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,611,194 control chromosomes in the GnomAD database, including 310,770 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.70 ( 38941 hom., cov: 28)
Exomes š‘“: 0.61 ( 271829 hom. )

Consequence

MYO9B
NM_004145.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0350
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 Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP7
Synonymous conserved (PhyloP=-0.035 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO9BNM_004145.4 linkc.3795T>C p.Pro1265Pro synonymous_variant Exon 22 of 40 ENST00000682292.1 NP_004136.2 Q13459-1B0I1T6Q8WVD2
MYO9BNM_001130065.2 linkc.3795T>C p.Pro1265Pro synonymous_variant Exon 22 of 40 NP_001123537.1 Q8WVD2Q4LE74

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO9BENST00000682292.1 linkc.3795T>C p.Pro1265Pro synonymous_variant Exon 22 of 40 NM_004145.4 ENSP00000507803.1 Q13459-1

Frequencies

GnomAD3 genomes
AF:
0.701
AC:
106221
AN:
151496
Hom.:
38885
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.921
Gnomad AMI
AF:
0.555
Gnomad AMR
AF:
0.737
Gnomad ASJ
AF:
0.488
Gnomad EAS
AF:
0.762
Gnomad SAS
AF:
0.658
Gnomad FIN
AF:
0.615
Gnomad MID
AF:
0.603
Gnomad NFE
AF:
0.585
Gnomad OTH
AF:
0.688
GnomAD3 exomes
AF:
0.655
AC:
158220
AN:
241726
Hom.:
53411
AF XY:
0.642
AC XY:
85155
AN XY:
132622
show subpopulations
Gnomad AFR exome
AF:
0.929
Gnomad AMR exome
AF:
0.805
Gnomad ASJ exome
AF:
0.487
Gnomad EAS exome
AF:
0.774
Gnomad SAS exome
AF:
0.633
Gnomad FIN exome
AF:
0.609
Gnomad NFE exome
AF:
0.582
Gnomad OTH exome
AF:
0.633
GnomAD4 exome
AF:
0.606
AC:
883996
AN:
1459580
Hom.:
271829
Cov.:
86
AF XY:
0.605
AC XY:
439290
AN XY:
726102
show subpopulations
Gnomad4 AFR exome
AF:
0.935
Gnomad4 AMR exome
AF:
0.799
Gnomad4 ASJ exome
AF:
0.480
Gnomad4 EAS exome
AF:
0.753
Gnomad4 SAS exome
AF:
0.638
Gnomad4 FIN exome
AF:
0.605
Gnomad4 NFE exome
AF:
0.582
Gnomad4 OTH exome
AF:
0.617
GnomAD4 genome
AF:
0.701
AC:
106331
AN:
151614
Hom.:
38941
Cov.:
28
AF XY:
0.702
AC XY:
51954
AN XY:
74040
show subpopulations
Gnomad4 AFR
AF:
0.921
Gnomad4 AMR
AF:
0.737
Gnomad4 ASJ
AF:
0.488
Gnomad4 EAS
AF:
0.762
Gnomad4 SAS
AF:
0.657
Gnomad4 FIN
AF:
0.615
Gnomad4 NFE
AF:
0.585
Gnomad4 OTH
AF:
0.683
Alfa
AF:
0.612
Hom.:
14027
Bravo
AF:
0.724
Asia WGS
AF:
0.695
AC:
2413
AN:
3478
EpiCase
AF:
0.580
EpiControl
AF:
0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.40
DANN
Benign
0.18
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs2279003; hg19: chr19-17306031; COSMIC: COSV68277217; COSMIC: COSV68277217; API