Variant chr17-36599704-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024308.4(DHRS11):c.616G>A(p.Ala206Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

DHRS11
NM_024308.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

DHRS11 (HGNC:28639): (dehydrogenase/reductase 11) Enables 17-beta-hydroxysteroid dehydrogenase (NADP+) activity; 17-beta-ketosteroid reductase activity; and 3-keto sterol reductase activity. Involved in steroid biosynthetic process. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

DHRS11 links:

DHRS11 (HGNC:):

DHRS11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS11	NM_024308.4 linkuse as main transcript	c.616G>A	p.Ala206Thr	missense_variant	5/7	ENST00000618403.5	NP_077284.2	Q6UWP2-1A0A024R0T1
DHRS11	XM_011525233.3 linkuse as main transcript	c.406G>A	p.Ala136Thr	missense_variant	4/6		XP_011523535.1
DHRS11	XM_005257658.4 linkuse as main transcript	c.583-268G>A		intron_variant			XP_005257715.1	Q6UWP2-3
DHRS11	XM_047436732.1 linkuse as main transcript	c.373-268G>A		intron_variant			XP_047292688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS11	ENST00000618403.5 linkuse as main transcript	c.616G>A	p.Ala206Thr	missense_variant	5/7	1	NM_024308.4	ENSP00000482704.1		Q6UWP2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251490

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135916

show subpopulations

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.616G>A (p.A206T) alteration is located in exon 5 (coding exon 5) of the DHRS11 gene. This alteration results from a G to A substitution at nucleotide position 616, causing the alanine (A) at amino acid position 206 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.0075

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.95

L;.;.

PrimateAI

Uncertain

0.56

Sift4G

Benign

0.50

T;T;T

Polyphen

0.14

B;.;.

Vest4

0.89

MutPred

0.53

Gain of helix (P = 0.132);.;.;

MVP

0.39

ClinPred

0.55

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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