rs34719006

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3

The NM_001374385.1(ATP8B1):​c.208G>T​(p.Asp70Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. D70N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ATP8B1
NM_001374385.1 missense

Scores

3
14
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.18
Variant links:
Genes affected
ATP8B1 (HGNC:3706): (ATPase phospholipid transporting 8B1) This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP2
Missense variant in the ATP8B1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 21 curated pathogenic missense variants (we use a threshold of 10). The gene has 24 curated benign missense variants. Trascript score misZ: 3.3227 (above the threshold of 3.09). GenCC associations: The gene is linked to progressive familial intrahepatic cholestasis type 1, cholestasis, intrahepatic, of pregnancy, 1.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP8B1NM_001374385.1 linkc.208G>T p.Asp70Tyr missense_variant Exon 3 of 28 ENST00000648908.2 NP_001361314.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP8B1ENST00000648908.2 linkc.208G>T p.Asp70Tyr missense_variant Exon 3 of 28 NM_001374385.1 ENSP00000497896.1 O43520

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251108
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135720
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461692
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74276
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-6.3
D;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.0030
D;.
Polyphen
1.0
D;D
Vest4
0.78
MutPred
0.42
Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP
0.81
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.73
gMVP
0.74

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.

Other links and lift over

dbSNP: rs34719006; hg19: chr18-55373793; API