Variant 17-36592074-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024308.4(DHRS11):c.65G>A(p.Gly22Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000564 in 1,240,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DHRS11
NM_024308.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS11	NM_024308.4 linkuse as main transcript	c.65G>A	p.Gly22Asp	missense_variant	1/7	ENST00000618403.5	NP_077284.2	Q6UWP2-1A0A024R0T1
DHRS11	XM_005257658.4 linkuse as main transcript	c.65G>A	p.Gly22Asp	missense_variant	1/6		XP_005257715.1	Q6UWP2-3
DHRS11	XM_011525233.3 linkuse as main transcript	c.65G>A	p.Gly22Asp	missense_variant	1/6		XP_011523535.1
DHRS11	XM_047436732.1 linkuse as main transcript	c.65G>A	p.Gly22Asp	missense_variant	1/5		XP_047292688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DHRS11	ENST00000618403.5 linkuse as main transcript	c.65G>A	p.Gly22Asp	missense_variant	1/7	1	NM_024308.4	ENSP00000482704.1	Q6UWP2-1
DHRS11	ENST00000611337.4 linkuse as main transcript	c.-88+86G>A		intron_variant		5		ENSP00000477603.1	Q6UWP2-2
DHRS11	ENST00000612205.1 linkuse as main transcript	n.160G>A		non_coding_transcript_exon_variant	1/3	2
DHRS11	ENST00000612538.1 linkuse as main transcript	n.65G>A		non_coding_transcript_exon_variant	1/5	5		ENSP00000482124.1	A0A087WYV4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152060

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

GnomAD4 exome

AF:

0.00000551

AC:

AN:

1088844

Hom.:

Cov.:

AF XY:

0.00000776

AC XY:

AN XY:

515574

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74256

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

Bravo

AF:

0.0000151

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

Apr 25, 2022

The c.65G>A (p.G22D) alteration is located in exon 1 (coding exon 1) of the DHRS11 gene. This alteration results from a G to A substitution at nucleotide position 65, causing the glycine (G) at amino acid position 22 to be replaced by an aspartic acid (D). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

M_CAP

Pathogenic

0.86

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

3.6

PrimateAI

Pathogenic

0.91

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.87

MutPred

0.91

Loss of MoRF binding (P = 0.0593);

MVP

0.75

ClinPred

0.69

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.90

gMVP

0.93

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