7-87402199-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_000443.4(ABCB4):āc.3737A>Cā(p.Gln1246Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000443.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461814Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727212
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Progressive familial intrahepatic cholestasis type 3 Uncertain:1
The c.3737A>C (p.Gln1246Pro) missense variant in ABCB4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gln1246Pro variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Gln at position 1246 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Gln1246Pro in ABCB4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.