18-79069417-G-T

Variant names:

• chr18-79069417-G-T
• rs1035000530
• NM_198531.5:c.7G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_198531.5(ATP9B):​c.7G>T​(p.Asp3Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000922 in 1,517,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000079 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATP9B NM_198531.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35300076).

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.7G>T	p.Asp3Tyr	missense	Exon 1 of 30	NP_940933.3
	ATP9B	NM_001306085.2		c.7G>T	p.Asp3Tyr	missense	Exon 1 of 29	NP_001293014.1	O43861-2
	ATP9B	NR_148360.2		n.24G>T		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.7G>T	p.Asp3Tyr	missense	Exon 1 of 30	ENSP00000398076.2	O43861-1
	ATP9B	ENST00000307671.12	TSL:1	c.7G>T	p.Asp3Tyr	missense	Exon 1 of 29	ENSP00000304500.7	O43861-2
	ATP9B	ENST00000586722.5	TSL:1	c.7G>T	p.Asp3Tyr	missense	Exon 1 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152238 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00 AC: 0 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: 0.00000146 AC: 2 AN: 1365472 Hom.: 0 Cov.: 31 AF XY: 0.00000296 AC XY: 2 AN XY: 675726

African (AFR) AF: 0.00 AC: 0 AN: 28176

American (AMR) AF: 0.0000324 AC: 1 AN: 30848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22734

East Asian (EAS) AF: 0.00 AC: 0 AN: 31388

South Asian (SAS) AF: 0.00 AC: 0 AN: 75312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068016

Other (OTH) AF: 0.0000179 AC: 1 AN: 55740

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152238 Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41480

American (AMR) AF: 0.000654 AC: 10 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.50
MutPred		0.37		Gain of MoRF binding (P = 0.032)
MVP		0.86
MPC		0.83
ClinPred		0.89	D
GERP RS		2.6
PromoterAI		-0.31	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.69
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs1035000530; hg19: chr18-76829417; COSMIC: COSV100302929; COSMIC: COSV100302929;