4-42485560-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006095.2(ATP8A1):​c.2260A>G​(p.Thr754Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ATP8A1
NM_006095.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71
Variant links:
Genes affected
ATP8A1 (HGNC:13531): (ATPase phospholipid transporting 8A1) The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use the free energy of ATP hydrolysis to drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily catalyzes transport of heavy metal ions. Another subfamily transports non-heavy metal ions (NMHI). The protein encoded by this gene is a member of the third subfamily of P-type ATPases and acts to transport amphipaths, such as phosphatidylserine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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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
ATP8A1NM_006095.2 linkuse as main transcriptc.2260A>G p.Thr754Ala missense_variant 25/37 ENST00000381668.9 NP_006086.1 Q9Y2Q0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATP8A1ENST00000381668.9 linkuse as main transcriptc.2260A>G p.Thr754Ala missense_variant 25/371 NM_006095.2 ENSP00000371084.5 Q9Y2Q0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsNov 15, 2024The c.2260A>G (p.T754A) alteration is located in exon 25 (coding exon 25) of the ATP8A1 gene. This alteration results from a A to G substitution at nucleotide position 2260, causing the threonine (T) at amino acid position 754 to be replaced by an alanine (A). 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
0.11
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.096
T;.
Eigen
Benign
-0.036
Eigen_PC
Benign
0.079
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
0.33
N;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.96
N;N
REVEL
Uncertain
0.48
Sift
Benign
0.048
D;D
Sift4G
Benign
0.24
T;T
Polyphen
0.37
B;.
Vest4
0.69
MutPred
0.47
Gain of helix (P = 0.0199);.;
MVP
0.57
MPC
1.4
ClinPred
0.66
D
GERP RS
5.2
Varity_R
0.22
gMVP
0.41

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.

Other links and lift over

dbSNP: rs1188905779; hg19: chr4-42487577; API