7-138088640-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005989.4(AKR1D1):āc.133A>Gā(p.Ile45Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,090 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
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
AKR1D1
NM_005989.4 missense
NM_005989.4 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 5.38
Genes affected
AKR1D1 (HGNC:388): (aldo-keto reductase family 1 member D1) The enzyme encoded by this gene is responsible for the catalysis of the 5-beta-reduction of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure. Deficiency of this enzyme may contribute to hepatic dysfunction. Three transcript variants encoding different isoforms have been found for this gene. Other variants may be present, but their full-length natures have not been determined yet. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.887
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKR1D1 | NM_005989.4 | c.133A>G | p.Ile45Val | missense_variant | 2/9 | ENST00000242375.8 | |
AKR1D1 | NM_001190907.2 | c.133A>G | p.Ile45Val | missense_variant | 2/8 | ||
AKR1D1 | NM_001190906.2 | c.133A>G | p.Ile45Val | missense_variant | 2/8 | ||
AKR1D1 | XM_047420763.1 | c.94-3128A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKR1D1 | ENST00000242375.8 | c.133A>G | p.Ile45Val | missense_variant | 2/9 | 1 | NM_005989.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251288Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135798
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461856Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727230
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2023 | The c.133A>G (p.I45V) alteration is located in exon 2 (coding exon 2) of the AKR1D1 gene. This alteration results from a A to G substitution at nucleotide position 133, causing the isoleucine (I) at amino acid position 45 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
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
T;D;D
Polyphen
0.84
.;.;P
Vest4
MutPred
Loss of stability (P = 0.0527);Loss of stability (P = 0.0527);Loss of stability (P = 0.0527);
MVP
MPC
0.30
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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