chr10-4995378-G-T

Variant names:

• chr10-4995378-G-T
• rs1554772797
• NM_001393392.1:c.787C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001393392.1(AKR1C2):​c.787C>A​(p.Arg263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKR1C2 NM_001393392.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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]

ENSG00000224251 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.787C>A	p.Arg263Ser	missense_variant	Exon 7 of 9	ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.787C>A	p.Arg263Ser	missense_variant	Exon 7 of 9	1	NM_001393392.1	ENSP00000370129.4
AKR1C2	ENST00000421196.7	c.709C>A	p.Arg237Ser	missense_variant	Exon 6 of 8	1		ENSP00000392694.2
AKR1C2	ENST00000460124.5	n.2247C>A		non_coding_transcript_exon_variant	Exon 6 of 8	5
ENSG00000224251	ENST00000451575.6	n.-110G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD3 exomes AF: 0.00000850 AC: 1 AN: 117652 Hom.: 0 AF XY: 0.0000164 AC XY: 1 AN XY: 61096

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: 0.00

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000242 AC: 35 AN: 1443370 Hom.: 0 Cov.: 31 AF XY: 0.0000238 AC XY: 17 AN XY: 715540

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: 0.0000309

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.65	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0068	T
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.76		Loss of MoRF binding (P = 0.0119);.;
MVP		0.74
MPC		3.3
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.97
gMVP		0.47

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: rs1554772797; hg19: chr10-5037570;