chr7-138088655-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005989.4(AKR1D1):c.148C>T(p.Arg50Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,904 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005989.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKR1D1 | NM_005989.4 | c.148C>T | p.Arg50Ter | stop_gained | 2/9 | ENST00000242375.8 | |
AKR1D1 | NM_001190907.2 | c.148C>T | p.Arg50Ter | stop_gained | 2/8 | ||
AKR1D1 | NM_001190906.2 | c.148C>T | p.Arg50Ter | stop_gained | 2/8 | ||
AKR1D1 | XM_047420763.1 | c.94-3113C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKR1D1 | ENST00000242375.8 | c.148C>T | p.Arg50Ter | stop_gained | 2/9 | 1 | NM_005989.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251148Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135716
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461836Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 727212
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74280
ClinVar
Submissions by phenotype
Congenital bile acid synthesis defect 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | May 08, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2017 | Loss-of-function variants in AKR1D1 are known to be pathogenic (PMID: 12970144, 19175828, 20522910, 21185810, 23679950). This variant has been reported in an individual affected with neonatal liver failure (PMID: 19175828). This gene is also known as SRD5B1 in the literature. This variant is present in population databases (rs749224036, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Arg50*) in the AKR1D1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at