10-5157733-C-G

Position:

• chr10-5157733-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395972.1(AKR1C8):​c.757G>C​(p.Gly253Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 472,110 control chromosomes in the GnomAD database, including 67,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22075 hom., cov: 32)
  • Exomes 𝑓: 0.52 (45414 hom.)
• Consequence: AKR1C8 NM_001395972.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00946632).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C8	NM_001395972.1	c.757G>C	p.Gly253Arg	missense_variant	7/9	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C8	ENST00000648824.2	c.757G>C	p.Gly253Arg	missense_variant	7/9		NM_001395972.1	ENSP00000496804.1
AKR1C8	ENST00000578467.2	n.786G>C		non_coding_transcript_exon_variant	7/8	2
AKR1C8	ENST00000584929.7	n.*423G>C		non_coding_transcript_exon_variant	8/10	6		ENSP00000496857.1
AKR1C8	ENST00000584929.7	n.*423G>C		3_prime_UTR_variant	8/10	6		ENSP00000496857.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80005 AN: 151898 Hom.: 22065 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.516 AC: 165043 AN: 320094 Hom.: 45414 Cov.: 0 AF XY: 0.503 AC XY: 90837 AN XY: 180758

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.527 AC: 80042 AN: 152016 Hom.: 22075 Cov.: 32 AF XY: 0.526 AC XY: 39052 AN XY: 74296

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.464

Alfa AF: 0.492 Hom.: 3095

Bravo AF: 0.509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.012
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0095	T
gMVP		0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1781935; hg19: chr10-5199934;