14-23955191-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021004.4(DHRS4):​c.285C>G​(p.Asp95Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DHRS4
NM_021004.4 missense

Scores

8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.569

Publications

0 publications found
Variant links:
Genes affected
DHRS4 (HGNC:16985): (dehydrogenase/reductase 4) Enables identical protein binding activity; oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Involved in several processes, including cellular ketone metabolic process; positive regulation of reactive oxygen species metabolic process; and steroid metabolic process. Located in nucleus and peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]
DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHRS4NM_021004.4 linkc.285C>G p.Asp95Glu missense_variant Exon 2 of 8 ENST00000313250.10 NP_066284.2 Q9BTZ2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DHRS4ENST00000313250.10 linkc.285C>G p.Asp95Glu missense_variant Exon 2 of 8 1 NM_021004.4 ENSP00000326219.5 Q9BTZ2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000205
AC:
3
AN:
1461084
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726826
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33458
American (AMR)
AF:
0.00
AC:
0
AN:
44670
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26072
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86152
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5712
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1111618
Other (OTH)
AF:
0.00
AC:
0
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.285C>G (p.D95E) alteration is located in exon 2 (coding exon 2) of the DHRS4 gene. This alteration results from a C to G substitution at nucleotide position 285, causing the aspartic acid (D) at amino acid position 95 to be replaced by a glutamic acid (E). 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
Uncertain
0.53
BayesDel_addAF
Uncertain
0.039
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.;D;.;.;.;.
Eigen
Benign
-0.090
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.60
D
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.44
T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Benign
1.5
L;L;.;L;L;L;L
PhyloP100
0.57
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.7
D;D;D;D;D;D;D
REVEL
Benign
0.24
Sift
Benign
0.040
D;T;T;D;D;D;D
Sift4G
Benign
0.080
T;T;T;T;T;T;T
Polyphen
0.84
P;P;P;P;.;D;D
Vest4
0.33
MutPred
0.49
Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);
MVP
0.86
MPC
0.39
ClinPred
0.98
D
GERP RS
-0.047
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.42
Mutation Taster
=81/19
polymorphism

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

Other links and lift over

dbSNP: rs1367816310; hg19: chr14-24424400; API