Variant 2-169091827-A-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_001376924.1(DHRS9):c.610A>G(p.Ile204Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,636 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

DHRS9
NM_001376924.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

Variant links:

Genes affected

DHRS9 (HGNC:16888): (dehydrogenase/reductase 9) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. This protein demonstrates oxidoreductase activity toward hydroxysteroids and is able to convert 3-alpha-tetrahydroprogesterone to dihydroxyprogesterone and 3-alpha-androstanediol to dihydroxyprogesterone in the cytoplasm, and may additionally function as a transcriptional repressor in the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DHRS9 links:

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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
DHRS9	NM_001376924.1 linkuse as main transcript	c.610A>G	p.Ile204Val	missense_variant	4/5	ENST00000674881.1	NP_001363853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS9	ENST00000674881.1 linkuse as main transcript	c.610A>G	p.Ile204Val	missense_variant	4/5		NM_001376924.1	ENSP00000502399.1		Q9BPW9-1
DHRS9	ENST00000602501.5 linkuse as main transcript	c.610A>G	p.Ile204Val	missense_variant	7/8	1		ENSP00000473337.1		Q9BPW9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727126

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 01, 2023

The c.610A>G (p.I204V) alteration is located in exon 7 (coding exon 3) of the DHRS9 gene. This alteration results from a A to G substitution at nucleotide position 610, causing the isoleucine (I) at amino acid position 204 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;.;T;.;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

.;.;T;.;D;.;T

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

1.7

L;L;.;L;.;L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.64

.;N;N;N;N;N;N

REVEL

Uncertain

0.55

Sift

Benign

0.23

.;T;T;T;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T;T;T

Polyphen

0.74

P;P;.;P;.;P;P

Vest4

0.34

MutPred

0.81

Loss of catalytic residue at P206 (P = 0.0303);Loss of catalytic residue at P206 (P = 0.0303);.;Loss of catalytic residue at P206 (P = 0.0303);.;Loss of catalytic residue at P206 (P = 0.0303);Loss of catalytic residue at P206 (P = 0.0303);

MVP

0.96

ClinPred

0.94

GERP RS

6.0

Varity_R

0.19

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over