17-68989915-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_080283.4(ABCA9):c.3853G>A(p.Ala1285Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000919 in 1,610,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000095 ( 0 hom. )
Consequence
ABCA9
NM_080283.4 missense
NM_080283.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 4.42
Genes affected
ABCA9 (HGNC:39): (ATP binding cassette subfamily A member 9) This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two transmembrane domains and two nucleotide binding folds. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This gene is a member of the ABC1 subfamily and is clustered with four other ABC1 family members on chromosome 17q24. Transcriptional expression of this gene is induced during monocyte differentiation into macrophages and is suppressed by cholesterol import. [provided by RefSeq, Jul 2008]
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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=0.11734933).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA9 | NM_080283.4 | c.3853G>A | p.Ala1285Thr | missense_variant | 30/39 | ENST00000340001.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA9 | ENST00000340001.9 | c.3853G>A | p.Ala1285Thr | missense_variant | 30/39 | 1 | NM_080283.4 | P1 | |
ABCA9-AS1 | ENST00000630625.1 | n.378-22068C>T | intron_variant, non_coding_transcript_variant | 5 | |||||
ABCA9 | ENST00000453985.6 | c.3739G>A | p.Ala1247Thr | missense_variant | 29/38 | 5 | |||
ABCA9 | ENST00000460872.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152200Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000769 AC: 19AN: 247230Hom.: 0 AF XY: 0.0000973 AC XY: 13AN XY: 133608
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GnomAD4 exome AF: 0.0000946 AC: 138AN: 1458240Hom.: 0 Cov.: 31 AF XY: 0.000101 AC XY: 73AN XY: 725398
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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.3853G>A (p.A1285T) alteration is located in exon 30 (coding exon 29) of the ABCA9 gene. This alteration results from a G to A substitution at nucleotide position 3853, causing the alanine (A) at amino acid position 1285 to be replaced by a threonine (T). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at