chr17-50658104-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003786.4(ABCC3):c.509G>A(p.Arg170His) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
ABCC3
NM_003786.4 missense
NM_003786.4 missense
Scores
3
2
14
Clinical Significance
Conservation
PhyloP100: 6.48
Genes affected
ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) 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. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3226778).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC3 | NM_003786.4 | c.509G>A | p.Arg170His | missense_variant | 5/31 | ENST00000285238.13 | |
ABCC3 | NM_001144070.2 | c.509G>A | p.Arg170His | missense_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC3 | ENST00000285238.13 | c.509G>A | p.Arg170His | missense_variant | 5/31 | 1 | NM_003786.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251470Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135910
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GnomAD4 exome AF: 0.000112 AC: 164AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.000111 AC XY: 81AN XY: 727228
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74322
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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 | Dec 12, 2023 | The c.509G>A (p.R170H) alteration is located in exon 5 (coding exon 5) of the ABCC3 gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Benign
D;T
Sift4G
Benign
T;T
Polyphen
P;B
Vest4
MutPred
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
MPC
0.22
ClinPred
D
GERP RS
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Splicing
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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