13-95053117-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005845.5(ABCC4):āc.3434A>Gā(p.Glu1145Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
ABCC4
NM_005845.5 missense
NM_005845.5 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 5.86
Genes affected
ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) 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. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC4 | NM_005845.5 | c.3434A>G | p.Glu1145Gly | missense_variant | 27/31 | ENST00000645237.2 | NP_005836.2 | |
ABCC4 | NM_001301829.2 | c.3293A>G | p.Glu1098Gly | missense_variant | 26/30 | NP_001288758.1 | ||
ABCC4 | XM_047430034.1 | c.3305A>G | p.Glu1102Gly | missense_variant | 27/31 | XP_047285990.1 | ||
ABCC4 | XM_047430035.1 | c.2885A>G | p.Glu962Gly | missense_variant | 24/28 | XP_047285991.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCC4 | ENST00000645237.2 | c.3434A>G | p.Glu1145Gly | missense_variant | 27/31 | NM_005845.5 | ENSP00000494609.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727196
GnomAD4 exome
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2
AN:
1461760
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31
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0
AN XY:
727196
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 04, 2024 | The c.3434A>G (p.E1145G) alteration is located in exon 27 (coding exon 27) of the ABCC4 gene. This alteration results from a A to G substitution at nucleotide position 3434, causing the glutamic acid (E) at amino acid position 1145 to be replaced by a glycine (G). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;.
REVEL
Pathogenic
Sift
Benign
.;D;.
Sift4G
Benign
.;T;.
Polyphen
D;D;B
Vest4
0.41
MutPred
Loss of stability (P = 0.0441);Loss of stability (P = 0.0441);.;
MVP
0.94
MPC
0.35
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.