rs771188283

Variant names:

• chr10-4963452-C-G
• rs771188283
• NM_001353.6:c.8C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-4963452-C-G
• chr10-4963452-C-T

Variant summary

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

The NM_001353.6(AKR1C1):​c.8C>G​(p.Ser3Trp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AKR1C1 NM_001353.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

Genes affected

AKR1C1 (HGNC:384): (aldo-keto reductase family 1 member C1) 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 reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

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=0.16872942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6	c.8C>G	p.Ser3Trp	missense_variant	Exon 1 of 9	ENST00000380872.9	NP_001344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C1	ENST00000380872.9	c.8C>G	p.Ser3Trp	missense_variant	Exon 1 of 9	1	NM_001353.6	ENSP00000370254.4
AKR1C1	ENST00000442997.5	c.2C>G	p.Ser1Trp	missense_variant	Exon 1 of 7	3		ENSP00000416415.1
AKR1C1	ENST00000477661.1	n.200C>G		non_coding_transcript_exon_variant	Exon 1 of 8	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251412 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.032
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.27
MutPred		0.38		Loss of disorder (P = 0.0048);
MVP		0.49
MPC		0.23
ClinPred		0.91	D
GERP RS		-0.99
Varity_R		0.099
gMVP		0.41

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: rs771188283; hg19: chr10-5005644;