19-1785167-G-A

Position:

chr19-1785167-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138813.4(ATP8B3):c.3524C>T(p.Pro1175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,577,128 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: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

ATP8B3
NM_138813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.309892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B3	NM_138813.4 linkuse as main transcript	c.3524C>T	p.Pro1175Leu	missense_variant	27/29	ENST00000310127.10	NP_620168.1	O60423-2
ATP8B3	NM_001178002.3 linkuse as main transcript	c.3413C>T	p.Pro1138Leu	missense_variant	27/29		NP_001171473.1	O60423-3
ATP8B3	NR_047593.3 linkuse as main transcript	n.3907C>T		non_coding_transcript_exon_variant	27/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP8B3	ENST00000310127.10 linkuse as main transcript	c.3524C>T	p.Pro1175Leu	missense_variant	27/29	1	NM_138813.4	ENSP00000311336.6	O60423-2
ATP8B3	ENST00000525591.5 linkuse as main transcript	c.3413C>T	p.Pro1138Leu	missense_variant	27/29	1		ENSP00000437115.1	O60423-3
ATP8B3	ENST00000531925.5 linkuse as main transcript	n.*3407C>T		non_coding_transcript_exon_variant	27/29	2		ENSP00000444334.1	F5GZM8
ATP8B3	ENST00000531925.5 linkuse as main transcript	n.*3407C>T		3_prime_UTR_variant	27/29	2		ENSP00000444334.1	F5GZM8

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000803

AC:

AN:

199158

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

107790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000169

Gnomad OTH exome

AF:

0.000198

GnomAD4 exome

AF:

0.0000800

AC:

114

AN:

1424938

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

705898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000527

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000932

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000498

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000830

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

Apr 15, 2024

The c.3524C>T (p.P1175L) alteration is located in exon 27 (coding exon 26) of the ATP8B3 gene. This alteration results from a C to T substitution at nucleotide position 3524, causing the proline (P) at amino acid position 1175 to be replaced by a leucine (L). 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

0.24

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Benign

0.13

Sift

Benign

0.19

T;T

Sift4G

Benign

0.23

T;T

Polyphen

1.0

D;.

Vest4

0.47

MVP

0.70

MPC

0.089

ClinPred

0.66

GERP RS

3.4

Varity_R

0.19

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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