chr17-50658133-C-G
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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):āc.538C>Gā(p.Leu180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,614,112 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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 33)
Exomes š: 0.000060 ( 0 hom. )
Consequence
ABCC3
NM_003786.4 missense
NM_003786.4 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 0.774
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=0.3559363).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC3 | NM_003786.4 | c.538C>G | p.Leu180Val | missense_variant | 5/31 | ENST00000285238.13 | |
ABCC3 | NM_001144070.2 | c.538C>G | p.Leu180Val | missense_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC3 | ENST00000285238.13 | c.538C>G | p.Leu180Val | missense_variant | 5/31 | 1 | NM_003786.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251482Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135916
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 727240
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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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 | Nov 10, 2022 | The c.538C>G (p.L180V) alteration is located in exon 5 (coding exon 5) of the ABCC3 gene. This alteration results from a C to G substitution at nucleotide position 538, causing the leucine (L) at amino acid position 180 to be replaced by a valine (V). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Loss of stability (P = 0.0676);Loss of stability (P = 0.0676);
MVP
MPC
0.42
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