1-154330424-C-A

Position:

• chr1-154330424-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001370597.1(ATP8B2):​c.60C>A​(p.Asp20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,461,816 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 (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: ATP8B2 NM_001370597.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

Genes affected

ATP8B2 (HGNC:13534): (ATPase phospholipid transporting 8B2) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17074266).
• BS2: High AC in GnomAdExome4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B2	NM_001370597.1	c.60C>A	p.Asp20Glu	missense_variant	3/28	ENST00000368489.6	NP_001357526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B2	ENST00000368489.6	c.60C>A	p.Asp20Glu	missense_variant	3/28	1	NM_001370597.1	ENSP00000357475.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000376 AC: 55 AN: 1461816 Hom.: 0 Cov.: 33 AF XY: 0.0000440 AC XY: 32 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000477

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.159C>A (p.D53E) alteration is located in exon 3 (coding exon 3) of the ATP8B2 gene. This alteration results from a C to A substitution at nucleotide position 159, causing the aspartic acid (D) at amino acid position 53 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.035
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.76	T
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.098
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.37	B;B
Vest4		0.34
MVP		0.27
MPC		0.48
ClinPred		0.90	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs1685943556; hg19: chr1-154302900;