18-79096627-G-A

Variant names:

• chr18-79096627-G-A
• rs144519079
• NM_198531.5:c.271G>A

Variant summary

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

The NM_198531.5(ATP9B):​c.271G>A​(p.Gly91Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP9B NM_198531.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21
• 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.271G>A	p.Gly91Ser	missense	Exon 2 of 30	NP_940933.3
	ATP9B	NM_001306085.2		c.271G>A	p.Gly91Ser	missense	Exon 2 of 29	NP_001293014.1	O43861-2
	ATP9B	NR_148360.2		n.288G>A		non_coding_transcript_exon	Exon 2 of 32

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP9B	ENST00000426216.6	TSL:5 MANE Select	c.271G>A	p.Gly91Ser	missense	Exon 2 of 30	ENSP00000398076.2	O43861-1
	ATP9B	ENST00000307671.12	TSL:1	c.271G>A	p.Gly91Ser	missense	Exon 2 of 29	ENSP00000304500.7	O43861-2
	ATP9B	ENST00000586722.5	TSL:1	c.271G>A	p.Gly91Ser	missense	Exon 2 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.24
Sift	Benign	0.45	T
Sift4G	Benign	0.63	T
Polyphen		0.10	B
Vest4		0.79
MutPred		0.47		Loss of sheet (P = 0.0817)
MVP		0.66
MPC		0.24
ClinPred		0.57	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.63
Mutation Taster		=83/17	polymorphism

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: rs144519079; hg19: chr18-76856627;