rs3207905

chr10-5001626-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393392.1(AKR1C2):c.140A>G(p.His47Arg) 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. 15/21 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKR1C2 NM_001393392.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27

Genes affected

AKR1C2 (HGNC:385): (aldo-keto reductase family 1 member C2) 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 using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. 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 two different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075125396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.140A>G	p.His47Arg	missense_variant	2/9	ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.140A>G	p.His47Arg	missense_variant	2/9	1	NM_001393392.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461416 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	4.3
Dann	Benign	0.36
DEOGEN2	Benign	0.044	T;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.49	T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-3.2	N;.;.;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	3.2	N;N;.;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;.;T
Sift4G	Benign	1.0	T;T;.;T
Polyphen		0.0	B;B;.;.
Vest4		0.16
MutPred		0.58		Gain of catalytic residue at H47 (P = 0.0475);Gain of catalytic residue at H47 (P = 0.0475);Gain of catalytic residue at H47 (P = 0.0475);Gain of catalytic residue at H47 (P = 0.0475);
MVP		0.15
MPC		0.14
ClinPred		0.19	T
GERP RS		0.17
Varity_R		0.19
gMVP		0.58

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

Other links and lift over

dbSNP: rs3207905; hg19: chr10-5043818;