Variant chr10-5096415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003739.6(AKR1C3):c.90G>A(p.Pro30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,612,162 control chromosomes in the GnomAD database, including 96,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8461 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87968 hom. )

Consequence

AKR1C3
NM_003739.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54

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]

AKR1C3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKR1C3	NM_003739.6 linkuse as main transcript	c.90G>A	p.Pro30=	synonymous_variant	2/9	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2 linkuse as main transcript	c.90G>A	p.Pro30=	synonymous_variant	2/9		NP_001240837.1
AKR1C3	NM_001253909.2 linkuse as main transcript	c.90G>A	p.Pro30=	synonymous_variant	2/3		NP_001240838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5 linkuse as main transcript	c.90G>A	p.Pro30=	synonymous_variant	2/9	1	NM_003739.6	ENSP00000369927	P4	P42330-1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48941

AN:

151886

Hom.:

8454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.281

GnomAD3 exomes

AF:

0.280

AC:

70005

AN:

250292

Hom.:

11547

AF XY:

0.279

AC XY:

37730

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.00191

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.336

AC:

490762

AN:

1460158

Hom.:

87968

Cov.:

AF XY:

0.332

AC XY:

240913

AN XY:

726318

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.172

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.00270

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.322

AC:

48984

AN:

152004

Hom.:

8461

Cov.:

AF XY:

0.320

AC XY:

23813

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.313

Hom.:

4817

Bravo

AF:

0.309

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

DANN

Benign

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over