12-122753766-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003677.5(DENR):c.65A>C(p.Lys22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,613,924 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

DENR
NM_003677.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.98

Publications

5 publications found

Variant links:

Genes affected

DENR (HGNC:2769): (density regulated re-initiation and release factor) This gene encodes a protein whose expression was found to increase in cultured cells at high density but not during growth arrest. This gene was also shown to have increased expression in cells overexpressing HER-2/neu proto-oncogene. The protein contains an SUI1 domain. In budding yeast, SUI1 is a translation initiation factor that along with eIF-2 and the initiator tRNA-Met, directs the ribosome to the proper translation start site. Proteins similar to SUI have been found in mammals, insects, and plants. [provided by RefSeq, Jul 2008]

DENR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014574766).

BP6

Variant 12-122753766-A-C is Benign according to our data. Variant chr12-122753766-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044403.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENR	NM_003677.5 link	c.65A>C	p.Lys22Thr	missense_variant	Exon 2 of 8	ENST00000280557.11	NP_003668.2	O43583A0A024RBR3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DENR	ENST00000280557.11 link	c.65A>C	p.Lys22Thr	missense_variant	Exon 2 of 8	1	NM_003677.5	ENSP00000280557.6	O43583
DENR	ENST00000455982.2 link	c.65A>C	p.Lys22Thr	missense_variant	Exon 2 of 8	5		ENSP00000413661.2	F8VVL1
DENR	ENST00000537955.1 link	n.178A>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
DENR	ENST00000539463.1 link	n.198A>C		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00110

AC:

273

AN:

249214

AF XY:

0.00109

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000743

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00147

AC:

2146

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1075

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000917

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000581

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00179

AC:

1988

AN:

1111862

Other (OTH)

AF:

0.00134

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

111

223

334

446

557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00113

AC:

172

AN:

152242

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41470

American (AMR)

AF:

0.00131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00185

AC:

126

AN:

68042

Other (OTH)

AF:

0.00192

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00105

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000259

AC:

ESP6500EA

AF:

0.00228

AC:

ExAC

AF:

0.00119

AC:

144

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DENR-related disorder

Benign:1

Dec 28, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

M;.

PhyloP100

3.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.25

Sift

Benign

0.19

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0050

B;P

Vest4

0.27

MVP

0.45

MPC

0.66

ClinPred

0.027

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.10

gMVP

0.39

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-122753766-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over