4-88097565-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004827.3(ABCG2):c.1535C>A(p.Thr512Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,836 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: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ABCG2
NM_004827.3 missense
NM_004827.3 missense
Scores
3
8
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.39
Genes affected
ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in 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 White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
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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, 0.811
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCG2 | ENST00000237612.8 | c.1535C>A | p.Thr512Asn | missense_variant | Exon 13 of 16 | 1 | NM_004827.3 | ENSP00000237612.3 | ||
ABCG2 | ENST00000515655.5 | c.1535C>A | p.Thr512Asn | missense_variant | Exon 13 of 16 | 1 | ENSP00000426917.1 | |||
ABCG2 | ENST00000650821.1 | c.1535C>A | p.Thr512Asn | missense_variant | Exon 14 of 17 | ENSP00000498246.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251070Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135666
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727220
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
D;P
Vest4
MutPred
Gain of catalytic residue at F511 (P = 0.6256);Gain of catalytic residue at F511 (P = 0.6256);
MVP
MPC
0.071
ClinPred
D
GERP RS
Varity_R
Splicing
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Calibrated prediction
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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