rs192981275

Variant names:

• chr9-96249759-C-G
• rs192981275
• NM_000197.2:c.481G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-96249759-C-G
• chr9-96249759-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000197.2(HSD17B3):​c.481G>C​(p.Val161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,624 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V161I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HSD17B3 NM_000197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 1 publications found

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]

ENSG00000285269 (HGNC:):

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35993487).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.481G>C	p.Val161Leu	missense	Exon 6 of 11	NP_000188.1	P37058-1
	HSD17B3-AS1	NR_146524.1		n.437C>G		non_coding_transcript_exon	Exon 3 of 3
	SLC35D2-HSD17B3	NR_182427.1		n.3248G>C		non_coding_transcript_exon	Exon 21 of 26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.481G>C	p.Val161Leu	missense	Exon 6 of 11	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.481G>C	p.Val161Leu	missense	Exon 6 of 10	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*2157G>C		non_coding_transcript_exon	Exon 17 of 22	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251374 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461624 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.55
Sift	Benign	0.099	T
Sift4G	Benign	0.080	T
Polyphen		0.82	P
Vest4		0.57
MutPred		0.67		Loss of sheet (P = 0.1158)
MVP		0.75
MPC		0.39
ClinPred		0.43	T
GERP RS		4.4
Varity_R		0.15
gMVP		0.58
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs192981275; hg19: chr9-99012041;