Genetic Variant MYO9B:p.Ser1011Ala (chr19-17192965-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004145.4(MYO9B):c.3031T>G(p.Ser1011Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,527,950 control chromosomes in the GnomAD database, including 160,502 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.54 ( 23732 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136770 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.707

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.439414E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4 link	c.3031T>G	p.Ser1011Ala	missense_variant	Exon 21 of 40	ENST00000682292.1	NP_004136.2	Q13459-1B0I1T6Q8WVD2
MYO9B	NM_001130065.2 link	c.3031T>G	p.Ser1011Ala	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>G	p.Ser1011Ala	missense_variant	Exon 21 of 40		NM_004145.4	ENSP00000507803.1		Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81315

AN:

151912

Hom.:

23693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.520

AC:

77418

AN:

148976

Hom.:

21811

AF XY:

0.509

AC XY:

40565

AN XY:

79694

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.770

Gnomad SAS exome

AF:

0.530

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.492

GnomAD4 exome

AF:

0.434

AC:

597690

AN:

1375920

Hom.:

136770

Cov.:

AF XY:

0.436

AC XY:

294343

AN XY:

674462

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.705

Gnomad4 ASJ exome

AF:

0.326

Gnomad4 EAS exome

AF:

0.748

Gnomad4 SAS exome

AF:

0.538

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.459

GnomAD4 genome

AF:

0.535

AC:

81405

AN:

152030

Hom.:

23732

Cov.:

AF XY:

0.540

AC XY:

40086

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.740

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.758

Gnomad4 SAS

AF:

0.560

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.527

Alfa

AF:

0.422

Hom.:

20720

Bravo

AF:

0.563

TwinsUK

AF:

0.402

AC:

1492

ALSPAC

AF:

0.397

AC:

1529

ESP6500AA

AF:

0.746

AC:

2939

ESP6500EA

AF:

0.417

AC:

3377

ExAC

AF:

0.403

AC:

39756

Asia WGS

AF:

0.622

AC:

2161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.58

DANN

Benign

0.19

DEOGEN2

Benign

0.0071

.;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.042

.;T;T;T

MetaRNN

Benign

0.0000024

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.7

N;.;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

1.7

.;.;N;.

REVEL

Benign

0.043

Sift

Benign

1.0

.;.;T;.

Sift4G

Benign

0.78

T;T;T;T

Vest4

0.035

MPC

0.27

ClinPred

0.0035

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over