Genetic Variant NM_003725.4:c.17C>T (chr12-56773869-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003725.4(HSD17B6):c.17C>T(p.Ala6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000994 in 1,570,928 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

HSD17B6
NM_003725.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.37

Publications

3 publications found

Variant links:

Genes affected

HSD17B6 (HGNC:23316): (hydroxysteroid 17-beta dehydrogenase 6) The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013]

HSD17B6 links:

ENSG00000309589 (HGNC:):

ENSG00000309589 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009281039).

BP6

Variant 12-56773869-C-T is Benign according to our data. Variant chr12-56773869-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2204832.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003725.4. 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
	HSD17B6	NM_003725.4	MANE Select	c.17C>T	p.Ala6Val	missense	Exon 2 of 5	NP_003716.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD17B6	ENST00000322165.1	TSL:1 MANE Select	c.17C>T	p.Ala6Val	missense	Exon 2 of 5	ENSP00000318631.1	O14756
HSD17B6	ENST00000859675.1		c.17C>T	p.Ala6Val	missense	Exon 2 of 6	ENSP00000529734.1
HSD17B6	ENST00000554150.5	TSL:5	c.17C>T	p.Ala6Val	missense	Exon 3 of 6	ENSP00000452273.1	O14756

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000710

AC:

160

AN:

225368

AF XY:

0.000636

show subpopulations

Gnomad AFR exome

AF:

0.000439

Gnomad AMR exome

AF:

0.000567

Gnomad ASJ exome

AF:

0.000542

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000200

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00112

GnomAD4 exome

AF:

0.00101

AC:

1432

AN:

1418624

Hom.:

Cov.:

AF XY:

0.000981

AC XY:

687

AN XY:

700336

show subpopulations

African (AFR)

AF:

0.000307

AC:

AN:

32530

American (AMR)

AF:

0.000831

AC:

AN:

39730

Ashkenazi Jewish (ASJ)

AF:

0.000426

AC:

AN:

23470

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39100

South Asian (SAS)

AF:

0.000111

AC:

AN:

80738

European-Finnish (FIN)

AF:

0.000192

AC:

AN:

52164

Middle Eastern (MID)

AF:

0.000360

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00121

AC:

1316

AN:

1086966

Other (OTH)

AF:

0.000702

AC:

AN:

58372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000847

AC:

129

AN:

152304

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41558

American (AMR)

AF:

0.00209

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68016

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000931

Hom.:

Bravo

AF:

0.00102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000758

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.025

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.19

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.58

PhyloP100

-1.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.27

Sift

Benign

0.61

Sift4G

Benign

0.60

Polyphen

0.0010

Vest4

0.15

MVP

0.16

MPC

0.11

ClinPred

0.0016

GERP RS

-8.4

Varity_R

0.028

gMVP

0.43

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over