chr10-5102630-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003739.6(AKR1C3):c.826C>T(p.Arg276Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,483,840 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00067 ( 3 hom. )
Consequence
AKR1C3
NM_003739.6 missense
NM_003739.6 missense
Scores
1
4
10
Clinical Significance
Conservation
PhyloP100: -0.381
Genes affected
AKR1C3 (HGNC:386): (aldo-keto reductase family 1 member C3) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15485898).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKR1C3 | NM_003739.6 | c.826C>T | p.Arg276Cys | missense_variant | 7/9 | ENST00000380554.5 | |
AKR1C3 | NM_001253908.2 | c.826C>T | p.Arg276Cys | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKR1C3 | ENST00000380554.5 | c.826C>T | p.Arg276Cys | missense_variant | 7/9 | 1 | NM_003739.6 | P4 | |
AKR1C3 | ENST00000439082.7 | c.826C>T | p.Arg276Cys | missense_variant | 7/9 | 5 | A1 | ||
AKR1C3 | ENST00000605149.5 | c.757C>T | p.Arg253Cys | missense_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000356 AC: 54AN: 151696Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.000400 AC: 44AN: 110038Hom.: 0 AF XY: 0.000414 AC XY: 23AN XY: 55606
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GnomAD4 exome AF: 0.000669 AC: 891AN: 1332028Hom.: 3 Cov.: 33 AF XY: 0.000680 AC XY: 441AN XY: 648800
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GnomAD4 genome ? AF: 0.000356 AC: 54AN: 151812Hom.: 0 Cov.: 29 AF XY: 0.000364 AC XY: 27AN XY: 74178
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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 | Aug 23, 2021 | The c.826C>T (p.R276C) alteration is located in exon 7 (coding exon 7) of the AKR1C3 gene. This alteration results from a C to T substitution at nucleotide position 826, causing the arginine (R) at amino acid position 276 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
REVEL
Benign
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;.;D
Vest4
MVP
MPC
0.081
ClinPred
T
GERP RS
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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