rs7097295

Positions:

• chr10-5162965-C-A
• chr10-5162965-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395972.1(AKR1C8):​c.149G>T​(p.Arg50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: AKR1C8 NM_001395972.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17248622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C8	NM_001395972.1	c.149G>T	p.Arg50Leu	missense_variant	2/9	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C8	ENST00000648824.2	c.149G>T	p.Arg50Leu	missense_variant	2/9		NM_001395972.1	ENSP00000496804	P1
AKR1C8	ENST00000650030.1	c.149G>T	p.Arg50Leu	missense_variant	2/4			ENSP00000497014
AKR1C8	ENST00000578467.2	n.232G>T		non_coding_transcript_exon_variant	2/8	2
AKR1C8	ENST00000584929.7	c.149G>T	p.Arg50Leu	missense_variant, NMD_transcript_variant	2/10			ENSP00000496857

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N
GERP RS		1.4
Varity_R		0.20
gMVP		0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7097295; hg19: chr10-5204928;