Genetic Variant ATP9B:p.Gly91Arg (chr18-79096627-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198531.5(ATP9B):c.271G>C(p.Gly91Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,613,428 control chromosomes in the GnomAD database, including 22 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G91S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 22 hom. )

Consequence

ATP9B
NM_198531.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21

Publications

2 publications found

Variant links:

Genes affected

ATP9B (HGNC:13541): (ATPase phospholipid transporting 9B (putative)) Predicted to enable ATPase-coupled intramembrane lipid transporter activity. Predicted to be involved in endocytosis; phospholipid translocation; and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in perinuclear region of cytoplasm and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ATP9B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008199632).

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198531.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP9B	NM_198531.5	MANE Select	c.271G>C	p.Gly91Arg	missense	Exon 2 of 30	NP_940933.3
ATP9B	NM_001306085.2		c.271G>C	p.Gly91Arg	missense	Exon 2 of 29	NP_001293014.1	O43861-2
ATP9B	NR_148360.2		n.288G>C		non_coding_transcript_exon	Exon 2 of 32

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP9B	ENST00000426216.6	TSL:5 MANE Select	c.271G>C	p.Gly91Arg	missense	Exon 2 of 30	ENSP00000398076.2	O43861-1
ATP9B	ENST00000307671.12	TSL:1	c.271G>C	p.Gly91Arg	missense	Exon 2 of 29	ENSP00000304500.7	O43861-2
ATP9B	ENST00000586722.5	TSL:1	c.271G>C	p.Gly91Arg	missense	Exon 2 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

564

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00871

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00353

AC:

881

AN:

249890

AF XY:

0.00337

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00475

Gnomad ASJ exome

AF:

0.00687

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.000743

Gnomad NFE exome

AF:

0.00497

Gnomad OTH exome

AF:

0.00510

GnomAD4 exome

AF:

0.00464

AC:

6781

AN:

1461162

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

3261

AN XY:

726826

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33466

American (AMR)

AF:

0.00540

AC:

241

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00666

AC:

174

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.000951

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.000768

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00530

AC:

5897

AN:

1111650

Other (OTH)

AF:

0.00492

AC:

297

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

316

632

949

1265

1581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<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:

0.00371

AC:

565

AN:

152266

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000915

AC:

AN:

41542

American (AMR)

AF:

0.00870

AC:

133

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00509

AC:

346

AN:

68024

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

140

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:

0.00515

Hom.:

Bravo

AF:

0.00410

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00323

AC:

392

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00544

EpiControl

AF:

0.00519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

7.2

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.72

REVEL

Benign

0.25

Sift

Benign

0.10

Sift4G

Benign

0.57

Polyphen

0.021

Vest4

0.61

MVP

0.68

MPC

0.28

ClinPred

0.028

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.73

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over