chr5-160602579-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025153.3(ATP10B):c.3361G>A(p.Val1121Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000164 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
ATP10B
NM_025153.3 missense, splice_region
NM_025153.3 missense, splice_region
Scores
1
9
3
Splicing: ADA: 0.9209
1
1
Clinical Significance
Conservation
PhyloP100: 5.95
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ATP10B | NM_025153.3 | c.3361G>A | p.Val1121Met | missense_variant, splice_region_variant | 21/26 | ENST00000327245.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP10B | ENST00000327245.10 | c.3361G>A | p.Val1121Met | missense_variant, splice_region_variant | 21/26 | 1 | NM_025153.3 | P1 | |
ATP10B | ENST00000642502.1 | c.3277G>A | p.Val1093Met | missense_variant, splice_region_variant | 16/21 | ||||
ATP10B | ENST00000523758.1 | n.527G>A | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248738Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134950
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461380Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726970
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GnomAD4 genome ? Cov.: 33
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?
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33
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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 | Oct 10, 2023 | The c.3361G>A (p.V1121M) alteration is located in exon 21 (coding exon 17) of the ATP10B gene. This alteration results from a G to A substitution at nucleotide position 3361, causing the valine (V) at amino acid position 1121 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
1.0
.;D
Vest4
0.75
MutPred
0.41
.;Gain of ubiquitination at K1119 (P = 0.1047);
MVP
0.92
MPC
0.34
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at