rs748546166

Variant names:

• chr6-33205324-C-A
• rs748546166
• NM_014234.5:c.374C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33205324-C-A
• chr6-33205324-C-T

Variant summary

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

The NM_014234.5(HSD17B8):​c.374C>A​(p.Ala125Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0000066 (0 hom., cov: 32)
• Consequence: HSD17B8 NM_014234.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

Genes affected

HSD17B8 (HGNC:3554): (hydroxysteroid 17-beta dehydrogenase 8) In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined. [provided by RefSeq, Jul 2008]

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=0.15517294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B8	NM_014234.5	c.374C>A	p.Ala125Asp	missense_variant	Exon 3 of 9	ENST00000374662.4	NP_055049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B8	ENST00000374662.4	c.374C>A	p.Ala125Asp	missense_variant	Exon 3 of 9	1	NM_014234.5	ENSP00000363794.3
HSD17B8	ENST00000469186.1	n.538C>A		non_coding_transcript_exon_variant	Exon 2 of 7	5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74372

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.13	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.21
Sift	Benign	0.47	T
Sift4G	Benign	0.70	T
Polyphen		0.13	B
Vest4		0.46
MutPred		0.67		Loss of methylation at K122 (P = 0.0549);
MVP		0.59
MPC		0.47
ClinPred		0.26	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.63

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: rs748546166; hg19: chr6-33173101;