Genetic Variant NM_004145.4:c.437C>A (chr19-17102154-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004145.4(MYO9B):c.437C>A(p.Ala146Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,434 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. A146V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.31

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04537919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	NM_004145.4	MANE Select	c.437C>A	p.Ala146Glu	missense	Exon 2 of 40	NP_004136.2
	MYO9B	NM_001130065.2		c.437C>A	p.Ala146Glu	missense	Exon 2 of 40	NP_001123537.1	Q13459-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYO9B	ENST00000682292.1	MANE Select	c.437C>A	p.Ala146Glu	missense	Exon 2 of 40	ENSP00000507803.1	Q13459-1
MYO9B	ENST00000595618.5	TSL:1	c.437C>A	p.Ala146Glu	missense	Exon 2 of 40	ENSP00000471457.1	Q13459-2
MYO9B	ENST00000594824.5	TSL:5	c.437C>A	p.Ala146Glu	missense	Exon 2 of 40	ENSP00000471367.1	M0R0P8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111862

Other (OTH)

AF:

0.00

AC:

AN:

60370

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

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.55

M_CAP

Benign

0.021

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

PhyloP100

5.3

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.020

REVEL

Benign

0.12

Sift

Benign

0.49

Sift4G

Benign

0.87

Vest4

0.16

MutPred

0.41

Gain of disorder (P = 0.023)

MVP

0.18

MPC

0.85

ClinPred

0.29

GERP RS

4.6

PromoterAI

-0.011

Neutral

(source)

gMVP

0.77

Mutation Taster

=75/25

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over