Variant 19-1784836-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138813.4(ATP8B3):c.3643A>C(p.Lys1215Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATP8B3
NM_138813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.247

Variant links:

Genes affected

ATP8B3 (HGNC:13535): (ATPase phospholipid transporting 8B3) 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 the other. This gene encodes member 3 of phospholipid-transporting ATPase 8B; other members of this protein family are located on chromosomes 1, 15 and 18. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ATP8B3 links:

ATP8B3 (HGNC:):

ATP8B3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15176606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B3	NM_138813.4 linkuse as main transcript	c.3643A>C	p.Lys1215Gln	missense_variant	28/29	ENST00000310127.10	NP_620168.1	O60423-2
ATP8B3	NM_001178002.3 linkuse as main transcript	c.3532A>C	p.Lys1178Gln	missense_variant	28/29		NP_001171473.1	O60423-3
ATP8B3	NR_047593.3 linkuse as main transcript	n.4026A>C		non_coding_transcript_exon_variant	28/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP8B3	ENST00000310127.10 linkuse as main transcript	c.3643A>C	p.Lys1215Gln	missense_variant	28/29	1	NM_138813.4	ENSP00000311336.6	O60423-2
ATP8B3	ENST00000525591.5 linkuse as main transcript	c.3532A>C	p.Lys1178Gln	missense_variant	28/29	1		ENSP00000437115.1	O60423-3
ATP8B3	ENST00000531925.5 linkuse as main transcript	n.*3526A>C		non_coding_transcript_exon_variant	28/29	2		ENSP00000444334.1	F5GZM8
ATP8B3	ENST00000531925.5 linkuse as main transcript	n.*3526A>C		3_prime_UTR_variant	28/29	2		ENSP00000444334.1	F5GZM8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236536

Hom.:

AF XY:

0.00000779

AC XY:

AN XY:

128448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.87e-7

AC:

AN:

1455216

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.3643A>C (p.K1215Q) alteration is located in exon 28 (coding exon 27) of the ATP8B3 gene. This alteration results from a A to C substitution at nucleotide position 3643, causing the lysine (K) at amino acid position 1215 to be replaced by a glutamine (Q). 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.8

DANN

Benign

0.93

DEOGEN2

Benign

0.071

T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.083

Sift

Benign

0.32

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.94

P;.

Vest4

0.26

MutPred

0.48

Loss of methylation at K1215 (P = 0.0058);.;

MVP

0.45

MPC

0.22

ClinPred

0.33

GERP RS

1.0

Varity_R

0.060

gMVP

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over