4-88101287-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004827.3(ABCG2):c.1310A>G(p.Gln437Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 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: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ABCG2
NM_004827.3 missense
NM_004827.3 missense
Scores
9
5
4
Clinical Significance
Conservation
PhyloP100: 7.57
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.926
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCG2 | NM_004827.3 | c.1310A>G | p.Gln437Arg | missense_variant | 11/16 | ENST00000237612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCG2 | ENST00000237612.8 | c.1310A>G | p.Gln437Arg | missense_variant | 11/16 | 1 | NM_004827.3 | P1 | |
ABCG2 | ENST00000515655.5 | c.1310A>G | p.Gln437Arg | missense_variant | 11/16 | 1 | |||
ABCG2 | ENST00000650821.1 | c.1310A>G | p.Gln437Arg | missense_variant | 12/17 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251386Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135864
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461880Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727244
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GnomAD4 genome ? Cov.: 32
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?
Cov.:
32
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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 | May 17, 2023 | The c.1310A>G (p.Q437R) alteration is located in exon 11 (coding exon 10) of the ABCG2 gene. This alteration results from a A to G substitution at nucleotide position 1310, causing the glutamine (Q) at amino acid position 437 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Benign
D;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of methylation at Q437 (P = 0.0186);Gain of methylation at Q437 (P = 0.0186);
MVP
MPC
0.20
ClinPred
D
GERP RS
Varity_R
Splicing
Name
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