Genetic Variant NM_004145.4:c.4363G>T (chr19-17200417-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004145.4(MYO9B):c.4363G>T(p.Gly1455Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000317 in 1,579,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1455S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.721

Publications

8 publications found

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]

MYO9B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11262882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4 link	c.4363G>T	p.Gly1455Cys	missense_variant	Exon 25 of 40	ENST00000682292.1	NP_004136.2	Q13459-1B0I1T6Q8WVD2
MYO9B	NM_001130065.2 link	c.4363G>T	p.Gly1455Cys	missense_variant	Exon 25 of 40		NP_001123537.1	Q8WVD2Q4LE74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1 link	c.4363G>T	p.Gly1455Cys	missense_variant	Exon 25 of 40		NM_004145.4	ENSP00000507803.1		Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706734

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32674

American (AMR)

AF:

0.00

AC:

AN:

38066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25598

East Asian (EAS)

AF:

0.00

AC:

AN:

38168

South Asian (SAS)

AF:

0.00

AC:

AN:

82302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093952

Other (OTH)

AF:

0.00

AC:

AN:

59136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.020

.;T;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.74

.;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.90

L;.;L;.

PhyloP100

0.72

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

.;.;N;.

REVEL

Benign

0.24

Sift

Benign

0.051

.;.;T;.

Sift4G

Benign

0.093

T;T;T;T

Polyphen

0.73

P;.;P;.

Vest4

0.18

MutPred

0.14

Gain of methylation at K1454 (P = 0.0253);Gain of methylation at K1454 (P = 0.0253);Gain of methylation at K1454 (P = 0.0253);Gain of methylation at K1454 (P = 0.0253);

MVP

0.46

MPC

0.53

ClinPred

0.18

GERP RS

-0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.55

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over