Genetic Variant AKR1C8:p.Cys209Ser (chr10-5158663-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001395972.1(AKR1C8):c.626G>C(p.Cys209Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000591 in 338,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Consequence

AKR1C8
NM_001395972.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.64

Publications

0 publications found

Variant links:

Genes affected

AKR1C8 (HGNC:23469): (aldo-keto reductase family 1 member C8) Predicted to enable D-threo-aldose 1-dehydrogenase activity; aldo-keto reductase (NADP) activity; and estradiol 17-beta-dehydrogenase activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AKR1C8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3835614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C8	NM_001395972.1 link	c.626G>C	p.Cys209Ser	missense_variant	Exon 6 of 9	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AKR1C8	ENST00000648824.2 link	c.626G>C	p.Cys209Ser	missense_variant	Exon 6 of 9		NM_001395972.1	ENSP00000496804.1	A0A3B3IRI8
AKR1C8	ENST00000584929.7 link	n.*292G>C		non_coding_transcript_exon_variant	Exon 7 of 10	6		ENSP00000496857.1	Q5T2L2
AKR1C8	ENST00000584929.7 link	n.*292G>C		3_prime_UTR_variant	Exon 7 of 10	6		ENSP00000496857.1	Q5T2L2
AKR1C8	ENST00000578467.2 link	n.719-863G>C		intron_variant	Intron 6 of 7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000591

AC:

AN:

338248

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

191044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9312

American (AMR)

AF:

0.00

AC:

AN:

31054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11110

East Asian (EAS)

AF:

0.00

AC:

AN:

11376

South Asian (SAS)

AF:

0.0000161

AC:

AN:

61952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2524

European-Non Finnish (NFE)

AF:

0.00000600

AC:

AN:

166764

Other (OTH)

AF:

0.00

AC:

AN:

15050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.67

PhyloP100

4.6

GERP RS

3.7

gMVP

0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over