17-69079220-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_080284.3(ABCA6):c.4742C>T(p.Thr1581Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,609,468 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 2 hom. )
Consequence
ABCA6
NM_080284.3 missense
NM_080284.3 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 8.10
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 Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.864
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCA6 | NM_080284.3 | c.4742C>T | p.Thr1581Ile | missense_variant | 38/39 | ENST00000284425.7 | NP_525023.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA6 | ENST00000284425.7 | c.4742C>T | p.Thr1581Ile | missense_variant | 38/39 | 1 | NM_080284.3 | ENSP00000284425 | P1 | |
ABCA6 | ENST00000446604.6 | n.2008C>T | non_coding_transcript_exon_variant | 17/18 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000168 AC: 42AN: 249780Hom.: 1 AF XY: 0.000222 AC XY: 30AN XY: 134908
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GnomAD4 exome AF: 0.000318 AC: 464AN: 1457226Hom.: 2 Cov.: 31 AF XY: 0.000316 AC XY: 229AN XY: 724680
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GnomAD4 genome AF: 0.000236 AC: 36AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74426
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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 | Dec 21, 2022 | The c.4742C>T (p.T1581I) alteration is located in exon 38 (coding exon 37) of the ABCA6 gene. This alteration results from a C to T substitution at nucleotide position 4742, causing the threonine (T) at amino acid position 1581 to be replaced by an isoleucine (I). 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
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
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