Variant chr17-36592043-C-G 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.34C>G(p.Arg12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000086 in 1,232,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

DHRS11
NM_024308.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

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.34C>G	p.Arg12Gly	missense_variant	1/7	ENST00000618403.5	NP_077284.2	Q6UWP2-1A0A024R0T1
DHRS11	XM_005257658.4 linkuse as main transcript	c.34C>G	p.Arg12Gly	missense_variant	1/6		XP_005257715.1	Q6UWP2-3
DHRS11	XM_011525233.3 linkuse as main transcript	c.34C>G	p.Arg12Gly	missense_variant	1/6		XP_011523535.1
DHRS11	XM_047436732.1 linkuse as main transcript	c.34C>G	p.Arg12Gly	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.34C>G	p.Arg12Gly	missense_variant	1/7	1	NM_024308.4	ENSP00000482704.1	Q6UWP2-1
DHRS11	ENST00000611337.4 linkuse as main transcript	c.-88+55C>G		intron_variant		5		ENSP00000477603.1	Q6UWP2-2
DHRS11	ENST00000612205.1 linkuse as main transcript	n.129C>G		non_coding_transcript_exon_variant	1/3	2
DHRS11	ENST00000612538.1 linkuse as main transcript	n.34C>G		non_coding_transcript_exon_variant	1/5	5		ENSP00000482124.1	A0A087WYV4

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000768

AC:

AN:

1080384

Hom.:

Cov.:

AF XY:

0.0000783

AC XY:

AN XY:

510798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000120

Gnomad4 ASJ exome

AF:

0.00169

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000151

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ExAC

AF:

0.0000731

AC:

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

Mar 04, 2024

The c.34C>G (p.R12G) alteration is located in exon 1 (coding exon 1) of the DHRS11 gene. This alteration results from a C to G substitution at nucleotide position 34, causing the arginine (R) at amino acid position 12 to be replaced by a glycine (G). 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

0.72

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

M_CAP

Pathogenic

0.71

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.66

MutationAssessor

Uncertain

2.5

PrimateAI

Pathogenic

0.88

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.65

MutPred

0.58

Loss of MoRF binding (P = 0.0433);

MVP

0.79

ClinPred

0.99

GERP RS

5.3

Varity_R

0.71

gMVP

0.87

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