13-95053117-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005845.5(ABCC4):ā€‹c.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

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86
Variant links:
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]

Genome browser will be placed here

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
ABCC4NM_005845.5 linkuse as main transcriptc.3434A>G p.Glu1145Gly missense_variant 27/31 ENST00000645237.2 NP_005836.2 O15439-1A8K2Q2
ABCC4NM_001301829.2 linkuse as main transcriptc.3293A>G p.Glu1098Gly missense_variant 26/30 NP_001288758.1 O15439-2A8K2Q2
ABCC4XM_047430034.1 linkuse as main transcriptc.3305A>G p.Glu1102Gly missense_variant 27/31 XP_047285990.1
ABCC4XM_047430035.1 linkuse as main transcriptc.2885A>G p.Glu962Gly missense_variant 24/28 XP_047285991.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCC4ENST00000645237.2 linkuse as main transcriptc.3434A>G p.Glu1145Gly missense_variant 27/31 NM_005845.5 ENSP00000494609.1 O15439-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461760
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingAmbry GeneticsDec 04, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.60
D;D;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
.;T;T
M_CAP
Pathogenic
0.38
D
MetaRNN
Uncertain
0.59
D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
3.3
M;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.6
.;D;.
REVEL
Pathogenic
0.69
Sift
Benign
0.049
.;D;.
Sift4G
Benign
0.15
.;T;.
Polyphen
0.98
D;D;B
Vest4
0.41
MutPred
0.55
Loss of stability (P = 0.0441);Loss of stability (P = 0.0441);.;
MVP
0.94
MPC
0.35
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.34
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-95705371; API