dbSNP rs577438787: ATP8B3:p.Ala1179Ser (chr19-1784944-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_138813.4(ATP8B3):c.3535G>T(p.Ala1179Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,608,698 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1179T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ATP8B3
NM_138813.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30349082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B3	NM_138813.4 link	c.3535G>T	p.Ala1179Ser	missense_variant, splice_region_variant	Exon 28 of 29	ENST00000310127.10	NP_620168.1	O60423-2
ATP8B3	NM_001178002.3 link	c.3424G>T	p.Ala1142Ser	missense_variant, splice_region_variant	Exon 28 of 29		NP_001171473.1	O60423-3
ATP8B3	NR_047593.3 link	n.3918G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 28 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP8B3	ENST00000310127.10 link	c.3535G>T	p.Ala1179Ser	missense_variant, splice_region_variant	Exon 28 of 29	1	NM_138813.4	ENSP00000311336.6	O60423-2
ATP8B3	ENST00000525591.5 link	c.3424G>T	p.Ala1142Ser	missense_variant, splice_region_variant	Exon 28 of 29	1		ENSP00000437115.1	O60423-3
ATP8B3	ENST00000531925.5 link	n.*3418G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 28 of 29	2		ENSP00000444334.1	F5GZM8
ATP8B3	ENST00000531925.5 link	n.*3418G>T		3_prime_UTR_variant	Exon 28 of 29	2		ENSP00000444334.1	F5GZM8

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151772

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000826

AC:

AN:

242002

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131508

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:

0.0000677

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456808

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724332

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:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74218

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.77

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.83

P;.

Vest4

0.32

MutPred

0.58

Gain of disorder (P = 0.052);.;

MVP

0.86

MPC

0.38

ClinPred

0.63

GERP RS

4.7

Varity_R

0.12

gMVP

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over