4-88097565-G-T

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

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.39
Variant links:
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]

Genome browser will be placed here

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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCG2NM_004827.3 linkc.1535C>A p.Thr512Asn missense_variant Exon 13 of 16 ENST00000237612.8 NP_004818.2 Q9UNQ0-1A1LUE4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCG2ENST00000237612.8 linkc.1535C>A p.Thr512Asn missense_variant Exon 13 of 16 1 NM_004827.3 ENSP00000237612.3 Q9UNQ0-1
ABCG2ENST00000515655.5 linkc.1535C>A p.Thr512Asn missense_variant Exon 13 of 16 1 ENSP00000426917.1 Q9UNQ0-2
ABCG2ENST00000650821.1 linkc.1535C>A p.Thr512Asn missense_variant Exon 14 of 17 ENSP00000498246.1 Q9UNQ0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251070
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135666
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461836
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
T;D
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.5
D;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0040
D;D
Sift4G
Benign
0.095
T;D
Polyphen
0.99
D;P
Vest4
0.67
MutPred
0.64
Gain of catalytic residue at F511 (P = 0.6256);Gain of catalytic residue at F511 (P = 0.6256);
MVP
0.68
MPC
0.071
ClinPred
0.81
D
GERP RS
3.8
Varity_R
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1002012563; hg19: chr4-89018717; API