rs758238903

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004827.3(ABCG2):​c.1115C>T​(p.Ser372Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,064 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABCG2
NM_004827.3 missense

Scores

10
6
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.36
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCG2NM_004827.3 linkc.1115C>T p.Ser372Phe missense_variant Exon 9 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.1115C>T p.Ser372Phe missense_variant Exon 9 of 16 1 NM_004827.3 ENSP00000237612.3 Q9UNQ0-1
ABCG2ENST00000515655.5 linkc.1115C>T p.Ser372Phe missense_variant Exon 9 of 16 1 ENSP00000426917.1 Q9UNQ0-2
ABCG2ENST00000650821.1 linkc.1115C>T p.Ser372Phe missense_variant Exon 10 of 17 ENSP00000498246.1 Q9UNQ0-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251386
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
.;T
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.025
T
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Pathogenic
0.83
D
MutationAssessor
Pathogenic
4.3
H;H
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-5.1
D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
1.0
D;D
Vest4
0.70
MVP
0.91
MPC
0.084
ClinPred
0.98
D
GERP RS
5.7
Varity_R
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs758238903; hg19: chr4-89034534; API