Variant 12-56773869-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/21 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2204832.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B6	NM_003725.4 linkuse as main transcript	c.17C>T	p.Ala6Val	missense_variant	2/5	ENST00000322165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B6	ENST00000322165.1 linkuse as main transcript	c.17C>T	p.Ala6Val	missense_variant	2/5	1	NM_003725.4	P1

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

GnomAD3 exomes

AF:

0.000710

AC:

160

AN:

225368

Hom.:

AF XY:

0.000636

AC XY:

AN XY:

121142

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 SAS exome

AF:

0.0000395

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

Gnomad4 AFR exome

AF:

0.000307

Gnomad4 AMR exome

AF:

0.000831

Gnomad4 ASJ exome

AF:

0.000426

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.000192

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.000702

GnomAD4 genome

AF:

0.000847

AC:

129

AN:

152304

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00102

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.025

DANN

Benign

0.53

DEOGEN2

Benign

0.19

T;T;T;T;T;T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.68

.;.;.;T;.;T;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.0093

T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.58

N;N;N;.;N;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

N;N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.61

T;T;T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T;T;T

Polyphen

0.0010

B;B;B;.;B;.;B

Vest4

0.15

MVP

0.16

MPC

0.11

ClinPred

0.0016

GERP RS

-8.4

Varity_R

0.028

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over