5-160565864-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025153.3(ATP10B):​c.3975G>T​(p.Lys1325Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ATP10B
NM_025153.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.279
Variant links:
Genes affected
ATP10B (HGNC:13543): (ATPase phospholipid transporting 10B (putative)) Enables glycosylceramide flippase activity and phosphatidylcholine flippase activity. Involved in lysosomal membrane organization. Located in endoplasmic reticulum. Is integral component of lysosomal membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13236916).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATP10BNM_025153.3 linkuse as main transcriptc.3975G>T p.Lys1325Asn missense_variant 26/26 ENST00000327245.10 NP_079429.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATP10BENST00000327245.10 linkuse as main transcriptc.3975G>T p.Lys1325Asn missense_variant 26/261 NM_025153.3 ENSP00000313600 P1O94823-1
ATP10BENST00000642502.1 linkuse as main transcriptc.3891G>T p.Lys1297Asn missense_variant 21/21 ENSP00000493802

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248290
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134724
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:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461232
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726976
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000189

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 GeneticsApr 11, 2023The c.3975G>T (p.K1325N) alteration is located in exon 26 (coding exon 22) of the ATP10B gene. This alteration results from a G to T substitution at nucleotide position 3975, causing the lysine (K) at amino acid position 1325 to be replaced by an asparagine (N). 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
0.14
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
10
DANN
Uncertain
0.99
DEOGEN2
Benign
0.035
.;T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
.;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
.;N
REVEL
Benign
0.030
Sift
Uncertain
0.0080
.;D
Sift4G
Uncertain
0.035
.;D
Polyphen
0.20
.;B
Vest4
0.099
MutPred
0.58
.;Loss of methylation at K1325 (P = 0.0016);
MVP
0.42
MPC
0.092
ClinPred
0.28
T
GERP RS
1.6
Varity_R
0.10
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs140341970; hg19: chr5-159992871; API