12-122753750-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003677.5(DENR):​c.49C>T​(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

DENR
NM_003677.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00200
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028110504).
BP6
Variant 12-122753750-C-T is Benign according to our data. Variant chr12-122753750-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2211353.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DENRNM_003677.5 linkc.49C>T p.Pro17Ser missense_variant Exon 2 of 8 ENST00000280557.11 NP_003668.2 O43583A0A024RBR3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DENRENST00000280557.11 linkc.49C>T p.Pro17Ser missense_variant Exon 2 of 8 1 NM_003677.5 ENSP00000280557.6 O43583
DENRENST00000455982.2 linkc.49C>T p.Pro17Ser missense_variant Exon 2 of 8 5 ENSP00000413661.2 F8VVL1
DENRENST00000537955.1 linkn.162C>T non_coding_transcript_exon_variant Exon 2 of 2 2
DENRENST00000539463.1 linkn.182C>T non_coding_transcript_exon_variant Exon 2 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249234
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135220
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461702
Hom.:
0
Cov.:
30
AF XY:
0.0000289
AC XY:
21
AN XY:
727132
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:
0.0000405
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 16, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
7.6
DANN
Benign
0.88
DEOGEN2
Benign
0.041
T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.50
T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.028
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.46
N;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.011
Sift
Benign
0.48
T;T
Sift4G
Benign
0.87
T;T
Polyphen
0.0
B;B
Vest4
0.11
MutPred
0.26
Gain of catalytic residue at P17 (P = 0);Gain of catalytic residue at P17 (P = 0);
MVP
0.13
MPC
0.53
ClinPred
0.030
T
GERP RS
-0.47
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.032
gMVP
0.32

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: rs757045169; hg19: chr12-123238297; API