17-36592146-G-A

Position:

• chr17-36592146-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024308.4(DHRS11):​c.137G>A​(p.Gly46Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000177 in 1,132,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: DHRS11 NM_024308.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.53

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10858208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS11	NM_024308.4	c.137G>A	p.Gly46Asp	missense_variant	1/7	ENST00000618403.5	NP_077284.2
DHRS11	XM_005257658.4	c.137G>A	p.Gly46Asp	missense_variant	1/6		XP_005257715.1
DHRS11	XM_011525233.3	c.137G>A	p.Gly46Asp	missense_variant	1/6		XP_011523535.1
DHRS11	XM_047436732.1	c.137G>A	p.Gly46Asp	missense_variant	1/5		XP_047292688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS11	ENST00000618403.5	c.137G>A	p.Gly46Asp	missense_variant	1/7	1	NM_024308.4	ENSP00000482704.1
DHRS11	ENST00000611337.4	c.-88+158G>A		intron_variant		5		ENSP00000477603.1
DHRS11	ENST00000612205.1	n.232G>A		non_coding_transcript_exon_variant	1/3	2
DHRS11	ENST00000612538.1	n.137G>A		non_coding_transcript_exon_variant	1/5	5		ENSP00000482124.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1132978 Hom.: 0 Cov.: 30 AF XY: 0.00000184 AC XY: 1 AN XY: 542098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000339

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.137G>A (p.G46D) 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 137, causing the glycine (G) at amino acid position 46 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	Benign	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.68	N
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.48		Gain of solvent accessibility (P = 0.0648);
MVP		0.43
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.41

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

Other links and lift over

dbSNP: rs1294934393; hg19: chr17-34948576;