rs1219708995

Variant names:

• chr18-79069519-C-T
• rs1219708995
• NM_198531.5:c.109C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-79069519-C-T
• chr18-79069519-C-A
• chr18-79069519-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198531.5(ATP9B):​c.109C>T​(p.Arg37Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,267,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ATP9B NM_198531.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15047985).

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.109C>T	p.Arg37Trp	missense	Exon 1 of 30	NP_940933.3
	ATP9B	NM_001306085.2		c.109C>T	p.Arg37Trp	missense	Exon 1 of 29	NP_001293014.1	O43861-2
	ATP9B	NR_148360.2		n.126C>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.109C>T	p.Arg37Trp	missense	Exon 1 of 30	ENSP00000398076.2	O43861-1
	ATP9B	ENST00000307671.12	TSL:1	c.109C>T	p.Arg37Trp	missense	Exon 1 of 29	ENSP00000304500.7	O43861-2
	ATP9B	ENST00000586722.5	TSL:1	c.109C>T	p.Arg37Trp	missense	Exon 1 of 5	ENSP00000466992.1	B4DJ94

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1267976 Hom.: 0 Cov.: 30 AF XY: 0.00000162 AC XY: 1 AN XY: 618702

African (AFR) AF: 0.00 AC: 0 AN: 25682

American (AMR) AF: 0.00 AC: 0 AN: 18590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20212

East Asian (EAS) AF: 0.00 AC: 0 AN: 27402

South Asian (SAS) AF: 0.00 AC: 0 AN: 62786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3700

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1017056

Other (OTH) AF: 0.00 AC: 0 AN: 51816

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.099
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.050
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.11
Sift	Benign	0.065	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.28
MutPred		0.29		Loss of solvent accessibility (P = 0.0199)
MVP		0.23
MPC		0.24
ClinPred		0.59	D
GERP RS		0.59
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.47
Mutation Taster		=75/25	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: rs1219708995; hg19: chr18-76829519;