rs11568639
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005845.5(ABCC4):c.3659G>A(p.Arg1220Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000614 in 1,613,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
ABCC4
NM_005845.5 missense
NM_005845.5 missense
Scores
3
12
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.86
Genes affected
ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]
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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, 0.779
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC4 | NM_005845.5 | c.3659G>A | p.Arg1220Gln | missense_variant | 29/31 | ENST00000645237.2 | NP_005836.2 | |
ABCC4 | NM_001301829.2 | c.3518G>A | p.Arg1173Gln | missense_variant | 28/30 | NP_001288758.1 | ||
ABCC4 | XM_047430034.1 | c.3530G>A | p.Arg1177Gln | missense_variant | 29/31 | XP_047285990.1 | ||
ABCC4 | XM_047430035.1 | c.3110G>A | p.Arg1037Gln | missense_variant | 26/28 | XP_047285991.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCC4 | ENST00000645237.2 | c.3659G>A | p.Arg1220Gln | missense_variant | 29/31 | NM_005845.5 | ENSP00000494609.1 |
Frequencies
GnomAD3 genomes AF: 0.0000527 AC: 8AN: 151784Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251318Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135828
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GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461646Hom.: 0 Cov.: 30 AF XY: 0.0000688 AC XY: 50AN XY: 727106
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GnomAD4 genome AF: 0.0000527 AC: 8AN: 151900Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74218
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
M;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;.
REVEL
Uncertain
Sift
Uncertain
.;D;.
Sift4G
Uncertain
.;D;.
Polyphen
D;D;D
Vest4
0.60
MVP
0.80
MPC
0.91
ClinPred
D
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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