18-79069427-C-G

Variant names:

• chr18-79069427-C-G
• rs747144142
• NM_198531.5:c.17C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198531.5(ATP9B):​c.17C>G​(p.Pro6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P6Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ATP9B NM_198531.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP9B	NM_198531.5	MANE Select	c.17C>G	p.Pro6Arg	missense	Exon 1 of 30	NP_940933.3
	ATP9B	NM_001306085.2		c.17C>G	p.Pro6Arg	missense	Exon 1 of 29	NP_001293014.1	O43861-2
	ATP9B	NR_148360.2		n.34C>G		non_coding_transcript_exon	Exon 1 of 32

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP9B	ENST00000426216.6	TSL:5 MANE Select	c.17C>G	p.Pro6Arg	missense	Exon 1 of 30	ENSP00000398076.2	O43861-1
	ATP9B	ENST00000307671.12	TSL:1	c.17C>G	p.Pro6Arg	missense	Exon 1 of 29	ENSP00000304500.7	O43861-2
	ATP9B	ENST00000586722.5	TSL:1	c.17C>G	p.Pro6Arg	missense	Exon 1 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Benign	0.091
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.44		Gain of MoRF binding (P = 0)
MVP		0.86
MPC		0.88
ClinPred		0.88	D
GERP RS		2.6
PromoterAI		0.28	Neutral
Varity_R		0.095
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747144142; hg19: chr18-76829427;