rs387906751

Positions:

• chr10-4991861-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP3_Moderate PP5

The NM_001393392.1(AKR1C2):​c.899A>C​(p.Asn300Thr) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 12)
• Consequence: AKR1C2 NM_001393392.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.64

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 3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862
• PP5: Variant 10-4991861-T-G is Pathogenic according to our data. Variant chr10-4991861-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 30066.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.899A>C	p.Asn300Thr	missense_variant	8/9	ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.899A>C	p.Asn300Thr	missense_variant	8/9	1	NM_001393392.1	ENSP00000370129	P1
AKR1C2	ENST00000421196.7	c.821A>C	p.Asn274Thr	missense_variant	7/8	1		ENSP00000392694
AKR1C2	ENST00000460124.5	n.2359A>C		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 12

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

46,XY disorder of sex development due to testicular 17,20-desmolase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 12, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.0053	T
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.23	B;B
Vest4		0.45
MutPred		0.76		Gain of helix (P = 0.1736);.;
MVP		0.67
MPC		2.5
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.54
gMVP		0.25

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: rs387906751; hg19: chr10-5034053;