rs2066479

Positions:

• chr9-96235528-C-A
• chr9-96235528-C-G
• chr9-96235528-C-T

Variant summary

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

The NM_000197.2(HSD17B3):​c.865G>T​(p.Gly289Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G289S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HSD17B3 NM_000197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

Genes affected

HSD17B3 (HGNC:5212): (hydroxysteroid 17-beta dehydrogenase 3) This isoform of 17 beta-hydroxysteroid dehydrogenase is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in male pseudohermaphroditism with gynecomastia. [provided by RefSeq, Jul 2008]

SLC35D2-HSD17B3 (HGNC:):

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=0.14333957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.865G>T	p.Gly289Cys	missense_variant	11/11	ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3632G>T		non_coding_transcript_exon_variant	26/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.865G>T	p.Gly289Cys	missense_variant	11/11	1	NM_000197.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.9
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.38
Sift	Benign	0.047	D;D
Sift4G	Uncertain	0.048	D;D
Polyphen		0.99	D;.
Vest4		0.15
MutPred		0.22		Loss of glycosylation at S288 (P = 0.0461);.;
MVP		0.76
MPC		0.31
ClinPred		0.34	T
GERP RS		-5.2
Varity_R		0.077
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2066479; hg19: chr9-98997810;