19-1783171-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138813.4(ATP8B3):āc.3760T>Cā(p.Phe1254Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
ATP8B3
NM_138813.4 missense
NM_138813.4 missense
Scores
3
13
3
Clinical Significance
Conservation
PhyloP100: 4.71
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]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP8B3 | NM_138813.4 | c.3760T>C | p.Phe1254Leu | missense_variant | 29/29 | ENST00000310127.10 | NP_620168.1 | |
ATP8B3 | NM_001178002.3 | c.3649T>C | p.Phe1217Leu | missense_variant | 29/29 | NP_001171473.1 | ||
ATP8B3 | NR_047593.3 | n.4143T>C | non_coding_transcript_exon_variant | 29/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP8B3 | ENST00000310127.10 | c.3760T>C | p.Phe1254Leu | missense_variant | 29/29 | 1 | NM_138813.4 | ENSP00000311336.6 | ||
ATP8B3 | ENST00000525591.5 | c.3649T>C | p.Phe1217Leu | missense_variant | 29/29 | 1 | ENSP00000437115.1 | |||
ATP8B3 | ENST00000531925.5 | n.*3643T>C | non_coding_transcript_exon_variant | 29/29 | 2 | ENSP00000444334.1 | ||||
ATP8B3 | ENST00000531925.5 | n.*3643T>C | 3_prime_UTR_variant | 29/29 | 2 | ENSP00000444334.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248610Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135102
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461584Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727058
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GnomAD4 genome Cov.: 31
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31
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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 | Jan 10, 2023 | The c.3760T>C (p.F1254L) alteration is located in exon 29 (coding exon 28) of the ATP8B3 gene. This alteration results from a T to C substitution at nucleotide position 3760, causing the phenylalanine (F) at amino acid position 1254 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of loop (P = 0.069);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at