Variant 19-1784856-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138813.4(ATP8B3):c.3623G>A(p.Arg1208Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ATP8B3
NM_138813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.999

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B3	NM_138813.4 linkuse as main transcript	c.3623G>A	p.Arg1208Gln	missense_variant	28/29	ENST00000310127.10	NP_620168.1	O60423-2
ATP8B3	NM_001178002.3 linkuse as main transcript	c.3512G>A	p.Arg1171Gln	missense_variant	28/29		NP_001171473.1	O60423-3
ATP8B3	NR_047593.3 linkuse as main transcript	n.4006G>A		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.3623G>A	p.Arg1208Gln	missense_variant	28/29	1	NM_138813.4	ENSP00000311336.6	O60423-2
ATP8B3	ENST00000525591.5 linkuse as main transcript	c.3512G>A	p.Arg1171Gln	missense_variant	28/29	1		ENSP00000437115.1	O60423-3
ATP8B3	ENST00000531925.5 linkuse as main transcript	n.*3506G>A		non_coding_transcript_exon_variant	28/29	2		ENSP00000444334.1	F5GZM8
ATP8B3	ENST00000531925.5 linkuse as main transcript	n.*3506G>A		3_prime_UTR_variant	28/29	2		ENSP00000444334.1	F5GZM8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

242654

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458618

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000702

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000248

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

Mar 28, 2024

The c.3623G>A (p.R1208Q) alteration is located in exon 28 (coding exon 27) of the ATP8B3 gene. This alteration results from a G to A substitution at nucleotide position 3623, causing the arginine (R) at amino acid position 1208 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

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

0.081

Eigen_PC

Benign

-0.087

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.39

Sift

Benign

0.13

T;T

Sift4G

Benign

0.079

T;T

Polyphen

1.0

D;.

Vest4

0.44

MutPred

0.61

Loss of methylation at R1208 (P = 0.0518);.;

MVP

0.77

MPC

0.46

ClinPred

0.90

GERP RS

4.7

Varity_R

0.15

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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