Variant 19-1783144-G-C 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.3787C>G(p.Leu1263Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ATP8B3
NM_138813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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:

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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
ATP8B3	NM_138813.4 linkuse as main transcript	c.3787C>G	p.Leu1263Val	missense_variant	29/29	ENST00000310127.10
ATP8B3	NM_001178002.3 linkuse as main transcript	c.3676C>G	p.Leu1226Val	missense_variant	29/29
ATP8B3	NR_047593.3 linkuse as main transcript	n.4170C>G		non_coding_transcript_exon_variant	29/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B3	ENST00000310127.10 linkuse as main transcript	c.3787C>G	p.Leu1263Val	missense_variant	29/29	1	NM_138813.4	A2	O60423-2
ATP8B3	ENST00000525591.5 linkuse as main transcript	c.3676C>G	p.Leu1226Val	missense_variant	29/29	1		P2	O60423-3
ATP8B3	ENST00000531925.5 linkuse as main transcript	c.*3670C>G		3_prime_UTR_variant, NMD_transcript_variant	29/29	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248756

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

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:

0.00000205

AC:

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Dec 17, 2021

The c.3787C>G (p.L1263V) alteration is located in exon 29 (coding exon 28) of the ATP8B3 gene. This alteration results from a C to G substitution at nucleotide position 3787, causing the leucine (L) at amino acid position 1263 to be replaced by a valine (V). 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

0.22

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;.

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Uncertain

-0.0019

MutationAssessor

Uncertain

2.9

M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

1.0

D;.

Vest4

0.27

MutPred

0.61

Gain of MoRF binding (P = 0.0805);.;

MVP

0.82

MPC

0.36

ClinPred

0.86

GERP RS

4.6

Varity_R

0.24

gMVP

0.72

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

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