Genetic Variant NM_004145.4:c.3031T>A (chr19-17192965-T-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004145.4(MYO9B):c.3031T>A(p.Ser1011Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000589 in 1,528,174 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.

Frequency

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

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.707

Publications

66 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12627709).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4 link	c.3031T>A	p.Ser1011Thr	missense_variant	Exon 21 of 40	ENST00000682292.1	NP_004136.2	Q13459-1B0I1T6Q8WVD2
MYO9B	NM_001130065.2 link	c.3031T>A	p.Ser1011Thr	missense_variant	Exon 21 of 40		NP_001123537.1	Q8WVD2Q4LE74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1 link	c.3031T>A	p.Ser1011Thr	missense_variant	Exon 21 of 40		NM_004145.4	ENSP00000507803.1		Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151964

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000134

AC:

AN:

148976

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000343

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000581

AC:

AN:

1376210

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

674618

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31282

American (AMR)

AF:

0.00

AC:

AN:

34856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24672

East Asian (EAS)

AF:

0.00

AC:

AN:

35232

South Asian (SAS)

AF:

0.00

AC:

AN:

78464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.00000564

AC:

AN:

1063498

Other (OTH)

AF:

0.0000351

AC:

AN:

56938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

AF:

0.00000658

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Alfa

AF:

0.00

Hom.:

51595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0070

.;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.085

.;T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

N;.;N;.

PhyloP100

0.71

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.33

.;.;N;.

REVEL

Benign

0.034

Sift

Benign

0.25

.;.;T;.

Sift4G

Benign

0.41

T;T;T;T

Vest4

0.076

MutPred

0.62

Loss of stability (P = 0.1145);Loss of stability (P = 0.1145);Loss of stability (P = 0.1145);Loss of stability (P = 0.1145);

MVP

0.14

MPC

0.30

ClinPred

0.014

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.30

Mutation Taster

=100/0

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