19-1785557-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138813.4(ATP8B3):c.3305G>A(p.Arg1102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ATP8B3
NM_138813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027051479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATP8B3	NM_138813.4 linkuse as main transcript	c.3305G>A	p.Arg1102His	missense_variant	26/29	ENST00000310127.10
ATP8B3	NM_001178002.3 linkuse as main transcript	c.3194G>A	p.Arg1065His	missense_variant	26/29
ATP8B3	NR_047593.3 linkuse as main transcript	n.3688G>A		non_coding_transcript_exon_variant	26/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B3	ENST00000310127.10 linkuse as main transcript	c.3305G>A	p.Arg1102His	missense_variant	26/29	1	NM_138813.4	A2	O60423-2
ATP8B3	ENST00000525591.5 linkuse as main transcript	c.3194G>A	p.Arg1065His	missense_variant	26/29	1		P2	O60423-3
ATP8B3	ENST00000531925.5 linkuse as main transcript	c.*3188G>A		3_prime_UTR_variant, NMD_transcript_variant	26/29	2
ATP8B3	ENST00000526847.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0000486

AC:

AN:

247008

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134508

show subpopulations

Gnomad AFR exome

AF:

0.000781

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

AF:

0.0000212

AC:

AN:

1460628

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726598

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000230

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.000178

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

Jun 09, 2022

The c.3305G>A (p.R1102H) alteration is located in exon 26 (coding exon 25) of the ATP8B3 gene. This alteration results from a G to A substitution at nucleotide position 3305, causing the arginine (R) at amino acid position 1102 to be replaced by a histidine (H). 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

0.073

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.73

Cadd

Benign

0.0010

Dann

Benign

0.73

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.070

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.040

Sift

Benign

0.53

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0040

B;.

Vest4

0.098

MVP

0.17

MPC

0.095

ClinPred

0.023

GERP RS

-9.0

Varity_R

0.017

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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