10-5097493-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003739.6(AKR1C3):​c.312G>C​(p.Lys104Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AKR1C3 NM_003739.6 missense
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082604796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.312G>C	p.Lys104Asn	missense_variant	Exon 3 of 9	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.312G>C	p.Lys104Asn	missense_variant	Exon 3 of 9		NP_001240837.1
AKR1C3	NM_001253909.2	c.312G>C	p.Lys104Asn	missense_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>C	p.Lys104Asn	missense_variant	Exon 3 of 9	1	NM_003739.6	ENSP00000369927.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 58127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.7
DANN	Benign	0.86
DEOGEN2	Benign	0.032	T;.;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;.;L
PhyloP100		-0.90
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.5	.;.;.;D
REVEL	Benign	0.011
Sift	Benign	0.039	.;.;.;D
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.0070	.;.;.;B
Vest4		0.25, 0.24, 0.25
MutPred		0.45		.;Loss of ubiquitination at K104 (P = 0.0141);.;Loss of ubiquitination at K104 (P = 0.0141);
MVP		0.22
MPC		0.012
ClinPred		0.19	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.27
Mutation Taster		=84/16	polymorphism

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;