chr17-68992208-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_080283.4(ABCA9):c.3683G>A(p.Arg1228Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,448,866 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: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
ABCA9
NM_080283.4 missense
NM_080283.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 4.07
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA9 | NM_080283.4 | c.3683G>A | p.Arg1228Lys | missense_variant | 28/39 | ENST00000340001.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA9 | ENST00000340001.9 | c.3683G>A | p.Arg1228Lys | missense_variant | 28/39 | 1 | NM_080283.4 | P1 | |
ABCA9-AS1 | ENST00000630625.1 | n.378-19775C>T | intron_variant, non_coding_transcript_variant | 5 | |||||
ABCA9 | ENST00000453985.6 | c.3569G>A | p.Arg1190Lys | missense_variant | 27/38 | 5 | |||
ABCA9 | ENST00000460872.1 | n.475G>A | non_coding_transcript_exon_variant | 1/3 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241702Hom.: 0 AF XY: 0.00000767 AC XY: 1AN XY: 130354
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1448866Hom.: 0 Cov.: 28 AF XY: 0.00000973 AC XY: 7AN XY: 719576
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GnomAD4 genome ? Cov.: 32
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Cov.:
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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 | Nov 10, 2022 | The c.3683G>A (p.R1228K) alteration is located in exon 28 (coding exon 27) of the ABCA9 gene. This alteration results from a G to A substitution at nucleotide position 3683, causing the arginine (R) at amino acid position 1228 to be replaced by a lysine (K). 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
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of methylation at R1228 (P = 0.0075);.;
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
DS_AG_spliceai
Position offset: 12
Find out detailed SpliceAI scores and Pangolin per-transcript scores at