Genetic Variant ATP9B:p.Asp3Asn (chr18-79069417-G-A) – 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.7G>A(p.Asp3Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000732 in 1,365,474 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D3E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ATP9B
NM_198531.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62

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=0.31111354).

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.7G>A	p.Asp3Asn	missense	Exon 1 of 30	NP_940933.3
ATP9B	NM_001306085.2		c.7G>A	p.Asp3Asn	missense	Exon 1 of 29	NP_001293014.1	O43861-2
ATP9B	NR_148360.2		n.24G>A		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.7G>A	p.Asp3Asn	missense	Exon 1 of 30	ENSP00000398076.2	O43861-1
ATP9B	ENST00000307671.12	TSL:1	c.7G>A	p.Asp3Asn	missense	Exon 1 of 29	ENSP00000304500.7	O43861-2
ATP9B	ENST00000586722.5	TSL:1	c.7G>A	p.Asp3Asn	missense	Exon 1 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

140570

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1365474

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675728

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28176

American (AMR)

AF:

0.00

AC:

AN:

30848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22734

East Asian (EAS)

AF:

0.0000319

AC:

AN:

31388

South Asian (SAS)

AF:

0.00

AC:

AN:

75312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068018

Other (OTH)

AF:

0.00

AC:

AN:

55740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.0059

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Benign

0.069

Eigen_PC

Benign

-0.013

FATHMM_MKL

Benign

0.034

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.4

PhyloP100

3.6

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.24

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.38

MutPred

0.20

Gain of MoRF binding (P = 0.0161)

MVP

0.73

MPC

0.37

ClinPred

0.85

GERP RS

2.6

PromoterAI

-0.39

Neutral

(source)

Varity_R

0.17

gMVP

0.56

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over