10-5158663-C-G

Variant names:

• chr10-5158663-C-G
• NM_001395972.1:c.626G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	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	Appris	UniProt
AKR1C8	ENST00000648824.2	c.626G>C	p.Cys209Ser	missense_variant	Exon 6 of 9		NM_001395972.1	ENSP00000496804.1
AKR1C8	ENST00000584929.7	n.*292G>C		non_coding_transcript_exon_variant	Exon 7 of 10	6		ENSP00000496857.1
AKR1C8	ENST00000584929.7	n.*292G>C		3_prime_UTR_variant	Exon 7 of 10	6		ENSP00000496857.1
AKR1C8	ENST00000578467.2	n.719-863G>C		intron_variant	Intron 6 of 7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000591 AC: 2 AN: 338248 Hom.: 0 Cov.: 0 AF XY: 0.0000105 AC XY: 2 AN XY: 191044

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: 0.0000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000600

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.67	T
GERP RS		3.7
gMVP		0.71

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-5200861;