14-24290993-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001136050.3(DHRS1):ā€‹c.808C>Gā€‹(p.Arg270Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000124 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DHRS1
NM_001136050.3 missense, splice_region

Scores

6
7
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.50
Variant links:
Genes affected
DHRS1 (HGNC:16445): (dehydrogenase/reductase 1) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family. The encoded enzyme contains a conserved catalytic domain and likely functions as an oxidoreductase. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]
NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHRS1NM_001136050.3 linkc.808C>G p.Arg270Gly missense_variant, splice_region_variant Exon 9 of 9 ENST00000288111.12 NP_001129522.1 Q96LJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DHRS1ENST00000288111.12 linkc.808C>G p.Arg270Gly missense_variant, splice_region_variant Exon 9 of 9 1 NM_001136050.3 ENSP00000288111.7 Q96LJ7

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152088
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461858
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727230
show subpopulations
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
AF:
0.00000658
AC:
1
AN:
152088
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Uncertain
0.46
D
MutationAssessor
Pathogenic
3.5
H;H
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Pathogenic
0.67
Sift
Uncertain
0.028
D;D
Sift4G
Benign
0.061
T;T
Polyphen
0.90
P;P
Vest4
0.73
MutPred
0.43
Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP
0.87
MPC
0.22
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.35
gMVP
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777525623; hg19: chr14-24760199; API