Menu
GeneBe

10-5099338-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003739.6(AKR1C3):c.459G>A(p.Lys153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,614,118 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 70 hom. )

Consequence

AKR1C3
NM_003739.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00800
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-5099338-G-A is Benign according to our data. Variant chr10-5099338-G-A is described in ClinVar as [Benign]. Clinvar id is 779103.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.008 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1C3NM_003739.6 linkuse as main transcriptc.459G>A p.Lys153= synonymous_variant 5/9 ENST00000380554.5
AKR1C3NM_001253908.2 linkuse as main transcriptc.459G>A p.Lys153= synonymous_variant 5/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1C3ENST00000380554.5 linkuse as main transcriptc.459G>A p.Lys153= synonymous_variant 5/91 NM_003739.6 P4P42330-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0167
AC:
2543
AN:
152124
Hom.:
68
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00682
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.00445
AC:
1119
AN:
251428
Hom.:
25
AF XY:
0.00347
AC XY:
471
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.0587
Gnomad AMR exome
AF:
0.00335
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000264
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00179
AC:
2617
AN:
1461876
Hom.:
70
Cov.:
31
AF XY:
0.00156
AC XY:
1131
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0614
Gnomad4 AMR exome
AF:
0.00378
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000926
Gnomad4 OTH exome
AF:
0.00389
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0167
AC:
2548
AN:
152242
Hom.:
68
Cov.:
32
AF XY:
0.0157
AC XY:
1172
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0578
Gnomad4 AMR
AF:
0.00681
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.00428
Hom.:
3
Bravo
AF:
0.0185
Asia WGS
AF:
0.00722
AC:
25
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
3.9
Dann
Benign
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1937839; hg19: chr10-5141530; API