chr17-69085133-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_080284.3(ABCA6):c.4079C>A(p.Pro1360His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
ABCA6
NM_080284.3 missense
NM_080284.3 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 7.50
Genes affected
ABCA6 (HGNC:36): (ATP binding cassette subfamily A member 6) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. 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 encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24 and may play a role in macrophage lipid homeostasis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.785
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCA6 | NM_080284.3 | c.4079C>A | p.Pro1360His | missense_variant | 32/39 | ENST00000284425.7 | NP_525023.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA6 | ENST00000284425.7 | c.4079C>A | p.Pro1360His | missense_variant | 32/39 | 1 | NM_080284.3 | ENSP00000284425 | P1 | |
ABCA6 | ENST00000446604.6 | n.1345C>A | non_coding_transcript_exon_variant | 11/18 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 248904Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134558
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1460588Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 726530
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74414
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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 | Feb 16, 2023 | The c.4079C>A (p.P1360H) alteration is located in exon 32 (coding exon 31) of the ABCA6 gene. This alteration results from a C to A substitution at nucleotide position 4079, causing the proline (P) at amino acid position 1360 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
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