14-24292315-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136050.3(DHRS1):​c.523G>A​(p.Ala175Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DHRS1
NM_001136050.3 missense

Scores

4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2937285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHRS1NM_001136050.3 linkc.523G>A p.Ala175Thr missense_variant Exon 6 of 9 ENST00000288111.12 NP_001129522.1 Q96LJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DHRS1ENST00000288111.12 linkc.523G>A p.Ala175Thr missense_variant Exon 6 of 9 1 NM_001136050.3 ENSP00000288111.7 Q96LJ7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250240
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135318
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461792
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727196
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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
0.0033
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
D;D
Eigen
Benign
-0.13
Eigen_PC
Benign
0.089
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Benign
1.0
L;L
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.28
Sift
Benign
0.17
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.020
B;B
Vest4
0.16
MutPred
0.51
Loss of stability (P = 0.1069);Loss of stability (P = 0.1069);
MVP
0.74
MPC
0.19
ClinPred
0.44
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.64

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

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

Other links and lift over

dbSNP: rs144351742; hg19: chr14-24761521; API