Genetic Variant ATP9B:p.Pro9Arg (chr18-79069436-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_198531.5(ATP9B):c.26C>G(p.Pro9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,366,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P9L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

ATP9B
NM_198531.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.888

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3817835).

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.26C>G	p.Pro9Arg	missense	Exon 1 of 30	NP_940933.3
ATP9B	NM_001306085.2		c.26C>G	p.Pro9Arg	missense	Exon 1 of 29	NP_001293014.1	O43861-2
ATP9B	NR_148360.2		n.43C>G		non_coding_transcript_exon	Exon 1 of 32

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP9B	ENST00000426216.6	TSL:5 MANE Select	c.26C>G	p.Pro9Arg	missense	Exon 1 of 30	ENSP00000398076.2	O43861-1
ATP9B	ENST00000307671.12	TSL:1	c.26C>G	p.Pro9Arg	missense	Exon 1 of 29	ENSP00000304500.7	O43861-2
ATP9B	ENST00000586722.5	TSL:1	c.26C>G	p.Pro9Arg	missense	Exon 1 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1366874

Hom.:

Cov.:

AF XY:

0.00000591

AC XY:

AN XY:

676454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28236

American (AMR)

AF:

0.00

AC:

AN:

30942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23378

East Asian (EAS)

AF:

0.0000324

AC:

AN:

30854

South Asian (SAS)

AF:

0.0000264

AC:

AN:

75620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4522

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1069138

Other (OTH)

AF:

0.00

AC:

AN:

55970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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

0.22

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.046

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.1

PhyloP100

0.89

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.15

REVEL

Benign

0.21

Sift

Benign

0.082

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.36

MutPred

0.45

Gain of MoRF binding (P = 3e-04)

MVP

0.81

MPC

0.87

ClinPred

0.90

GERP RS

1.7

PromoterAI

-0.062

Neutral

(source)

Varity_R

0.021

gMVP

0.66

Mutation Taster

=85/15

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