Variant 14-24291558-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001136050.3(DHRS1):c.722C>T(p.Thr241Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0683 in 1,613,984 control chromosomes in the GnomAD database, including 4,223 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.085 ( 611 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3612 hom. )

Consequence

DHRS1
NM_001136050.3 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.80

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]

DHRS1 links:

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]

NOP9 links:

ENSG00000288044 (HGNC:):

ENSG00000288044 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS1	NM_001136050.3 link	c.722C>T	p.Thr241Ile	missense_variant, splice_region_variant	Exon 7 of 9	ENST00000288111.12	NP_001129522.1	Q96LJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS1	ENST00000288111.12 link	c.722C>T	p.Thr241Ile	missense_variant, splice_region_variant	Exon 7 of 9	1	NM_001136050.3	ENSP00000288111.7		Q96LJ7

Frequencies

GnomAD3 genomes

AF:

0.0853

AC:

12982

AN:

152116

Hom.:

611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0652

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0746

Gnomad SAS

AF:

0.0953

Gnomad FIN

AF:

0.0535

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0670

Gnomad OTH

AF:

0.0756

GnomAD3 exomes

AF:

0.0754

AC:

18951

AN:

251492

Hom.:

818

AF XY:

0.0768

AC XY:

10436

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0623

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0838

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0649

Gnomad OTH exome

AF:

0.0752

GnomAD4 exome

AF:

0.0665

AC:

97237

AN:

1461750

Hom.:

3612

Cov.:

AF XY:

0.0682

AC XY:

49594

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0647

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.0605

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.0510

Gnomad4 NFE exome

AF:

0.0616

Gnomad4 OTH exome

AF:

0.0709

GnomAD4 genome

AF:

0.0853

AC:

12988

AN:

152234

Hom.:

611

Cov.:

AF XY:

0.0850

AC XY:

6331

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0653

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0744

Gnomad4 SAS

AF:

0.0956

Gnomad4 FIN

AF:

0.0535

Gnomad4 NFE

AF:

0.0670

Gnomad4 OTH

AF:

0.0748

Alfa

AF:

0.0732

Hom.:

1056

Bravo

AF:

0.0866

TwinsUK

AF:

0.0529

AC:

196

ALSPAC

AF:

0.0599

AC:

231

ESP6500AA

AF:

0.124

AC:

545

ESP6500EA

AF:

0.0700

AC:

602

ExAC

AF:

0.0759

AC:

9209

Asia WGS

AF:

0.0750

AC:

259

AN:

3478

EpiCase

AF:

0.0707

EpiControl

AF:

0.0670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.38

Sift

Benign

0.065

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.34

B;B

Vest4

0.12

MPC

0.19

ClinPred

0.033

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: -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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over