NM_003739.6:c.312G>A

Variant names:

• chr10-5097493-G-A
• rs12387
• NM_003739.6:c.312G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003739.6(AKR1C3):​c.312G>A​(p.Lys104Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,613,590 control chromosomes in the GnomAD database, including 557,957 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 0.84 (54218 hom., cov: 31)
  • Exomes 𝑓: 0.83 (503739 hom.)
• Consequence: AKR1C3 NM_003739.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 45 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-0.898 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.312G>A	p.Lys104Lys	synonymous_variant	Exon 3 of 9	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.312G>A	p.Lys104Lys	synonymous_variant	Exon 3 of 9		NP_001240837.1
AKR1C3	NM_001253909.2	c.312G>A	p.Lys104Lys	synonymous_variant	Exon 3 of 3		NP_001240838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.312G>A	p.Lys104Lys	synonymous_variant	Exon 3 of 9	1	NM_003739.6	ENSP00000369927.3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128299 AN: 151984 Hom.: 54167 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.876

GnomAD2 exomes AF: 0.836 AC: 210169 AN: 251356 AF XY: 0.837

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.800

Gnomad ASJ exome AF: 0.888

Gnomad EAS exome AF: 0.865

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.838

GnomAD4 exome AF: 0.830 AC: 1212755 AN: 1461490 Hom.: 503739 Cov.: 51 AF XY: 0.831 AC XY: 604304 AN XY: 727072

African (AFR) AF: 0.874 AC: 29233 AN: 33458

American (AMR) AF: 0.796 AC: 35603 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 23296 AN: 26126

East Asian (EAS) AF: 0.884 AC: 35094 AN: 39686

South Asian (SAS) AF: 0.854 AC: 73641 AN: 86244

European-Finnish (FIN) AF: 0.830 AC: 44309 AN: 53412

Middle Eastern (MID) AF: 0.909 AC: 5238 AN: 5764

European-Non Finnish (NFE) AF: 0.824 AC: 915607 AN: 1111704

Other (OTH) AF: 0.840 AC: 50734 AN: 60378

GnomAD4 genome AF: 0.844 AC: 128405 AN: 152100 Hom.: 54218 Cov.: 31 AF XY: 0.843 AC XY: 62679 AN XY: 74344

African (AFR) AF: 0.871 AC: 36154 AN: 41494

American (AMR) AF: 0.816 AC: 12463 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3082 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4488 AN: 5172

South Asian (SAS) AF: 0.846 AC: 4082 AN: 4824

European-Finnish (FIN) AF: 0.828 AC: 8741 AN: 10554

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56478 AN: 68002

Other (OTH) AF: 0.877 AC: 1848 AN: 2108

Alfa AF: 0.839 Hom.: 58127

Bravo AF: 0.845

Asia WGS AF: 0.862 AC: 2998 AN: 3478

EpiCase AF: 0.839

EpiControl AF: 0.835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.31
DANN	Benign	0.63
PhyloP100		-0.90
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12387; hg19: chr10-5139685; COSMIC: COSV108232352; COSMIC: COSV108232352;