9-96302014-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000197.2(HSD17B3):​c.91G>A​(p.Val31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,124 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 31)
Exomes 𝑓: 0.012 ( 323 hom. )

Consequence

HSD17B3
NM_000197.2 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.34
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0019617677).
BP6
Variant 9-96302014-C-T is Benign according to our data. Variant chr9-96302014-C-T is described in ClinVar as [Benign]. Clinvar id is 367684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-96302014-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSD17B3NM_000197.2 linkuse as main transcriptc.91G>A p.Val31Ile missense_variant 1/11 ENST00000375263.8 NP_000188.1
SLC35D2-HSD17B3NR_182427.1 linkuse as main transcriptn.2858G>A non_coding_transcript_exon_variant 16/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSD17B3ENST00000375263.8 linkuse as main transcriptc.91G>A p.Val31Ile missense_variant 1/111 NM_000197.2 ENSP00000364412 P1P37058-1

Frequencies

GnomAD3 genomes
AF:
0.0121
AC:
1838
AN:
152164
Hom.:
28
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0121
Gnomad AMI
AF:
0.0219
Gnomad AMR
AF:
0.00897
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.0566
Gnomad SAS
AF:
0.0615
Gnomad FIN
AF:
0.00461
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00727
Gnomad OTH
AF:
0.0119
GnomAD3 exomes
AF:
0.0177
AC:
4457
AN:
251448
Hom.:
128
AF XY:
0.0193
AC XY:
2628
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.0119
Gnomad AMR exome
AF:
0.00431
Gnomad ASJ exome
AF:
0.00397
Gnomad EAS exome
AF:
0.0644
Gnomad SAS exome
AF:
0.0600
Gnomad FIN exome
AF:
0.00522
Gnomad NFE exome
AF:
0.00753
Gnomad OTH exome
AF:
0.0135
GnomAD4 exome
AF:
0.0118
AC:
17210
AN:
1461842
Hom.:
323
Cov.:
33
AF XY:
0.0132
AC XY:
9617
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0109
Gnomad4 AMR exome
AF:
0.00537
Gnomad4 ASJ exome
AF:
0.00386
Gnomad4 EAS exome
AF:
0.0538
Gnomad4 SAS exome
AF:
0.0600
Gnomad4 FIN exome
AF:
0.00616
Gnomad4 NFE exome
AF:
0.00716
Gnomad4 OTH exome
AF:
0.0143
GnomAD4 genome
AF:
0.0121
AC:
1842
AN:
152282
Hom.:
29
Cov.:
31
AF XY:
0.0128
AC XY:
956
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0122
Gnomad4 AMR
AF:
0.00895
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.0567
Gnomad4 SAS
AF:
0.0612
Gnomad4 FIN
AF:
0.00461
Gnomad4 NFE
AF:
0.00728
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00918
Hom.:
50
Bravo
AF:
0.0119
TwinsUK
AF:
0.00809
AC:
30
ALSPAC
AF:
0.00519
AC:
20
ESP6500AA
AF:
0.00908
AC:
40
ESP6500EA
AF:
0.00767
AC:
66
ExAC
AF:
0.0190
AC:
2309
Asia WGS
AF:
0.0580
AC:
201
AN:
3478
EpiCase
AF:
0.00671
EpiControl
AF:
0.00717

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 04, 2018- -
Testosterone 17-beta-dehydrogenase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
0.49
DANN
Benign
0.25
DEOGEN2
Benign
0.081
T;.;.;T
Eigen
Benign
-2.3
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.0024
N
LIST_S2
Benign
0.32
T;T;T;T
MetaRNN
Benign
0.0020
T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
-1.1
N;N;.;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.10
N;N;.;.
REVEL
Benign
0.20
Sift
Benign
1.0
T;T;.;.
Sift4G
Benign
0.84
T;T;.;.
Polyphen
0.0
B;.;.;.
Vest4
0.033
MPC
0.13
ClinPred
0.0011
T
GERP RS
-9.6
Varity_R
0.018
gMVP
0.35

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2066480; hg19: chr9-99064296; COSMIC: COSV64558824; API