17-36598181-A-G

Position:

• chr17-36598181-A-G

Variant summary

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

The NM_024308.4(DHRS11):​c.376A>G​(p.Ser126Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DHRS11 NM_024308.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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 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	c.376A>G	p.Ser126Gly	missense_variant	3/7	ENST00000618403.5	NP_077284.2
DHRS11	XM_005257658.4	c.376A>G	p.Ser126Gly	missense_variant	3/6		XP_005257715.1
DHRS11	XM_011525233.3	c.166A>G	p.Ser56Gly	missense_variant	2/6		XP_011523535.1
DHRS11	XM_047436732.1	c.166A>G	p.Ser56Gly	missense_variant	2/5		XP_047292688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS11	ENST00000618403.5	c.376A>G	p.Ser126Gly	missense_variant	3/7	1	NM_024308.4	ENSP00000482704.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 23, 2023

The c.376A>G (p.S126G) alteration is located in exon 3 (coding exon 3) of the DHRS11 gene. This alteration results from a A to G substitution at nucleotide position 376, causing the serine (S) at amino acid position 126 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	Benign	0.15
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Uncertain	0.64	T
Sift4G	Uncertain	0.038	D;D;T;D
Polyphen		0.97	D;.;.;.
Vest4		0.75
MutPred		0.53		Loss of stability (P = 0.0646);.;.;.;
MVP		0.65
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.40
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-34954610;