12-15957007-C-T

Variant summary

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

The ENST00000526530(DERA):​c.-162C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

DERA
ENST00000526530 5_prime_UTR_premature_start_codon_gain

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
Variant links:
Genes affected
DERA (HGNC:24269): (deoxyribose-phosphate aldolase) Enables deoxyribose-phosphate aldolase activity. Involved in deoxyribonucleoside catabolic process. Located in nucleoplasm. [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=0.31814343).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DERANM_015954.4 linkc.103C>T p.Arg35Cys missense_variant Exon 2 of 9 ENST00000428559.7 NP_057038.2 Q9Y315
DERAXM_024449001.2 linkc.-162C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 9 XP_024304769.1
DERANM_001300779.2 linkc.103C>T p.Arg35Cys missense_variant Exon 2 of 8 NP_001287708.1 E9PPM8
DERAXM_024449001.2 linkc.-162C>T 5_prime_UTR_variant Exon 2 of 9 XP_024304769.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DERAENST00000428559.7 linkc.103C>T p.Arg35Cys missense_variant Exon 2 of 9 1 NM_015954.4 ENSP00000416583.2 Q9Y315

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249080
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135132
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:
0.0000266
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461636
Hom.:
0
Cov.:
30
AF XY:
0.0000234
AC XY:
17
AN XY:
727106
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:
0.0000288
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000555
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.103C>T (p.R35C) alteration is located in exon 2 (coding exon 2) of the DERA gene. This alteration results from a C to T substitution at nucleotide position 103, causing the arginine (R) at amino acid position 35 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;T;T
Eigen
Benign
-0.027
Eigen_PC
Benign
0.065
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.7
M;.;.
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-5.7
D;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.0090
D;D;D
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
0.0090
B;.;.
Vest4
0.43
MutPred
0.48
Loss of MoRF binding (P = 0.0101);.;Loss of MoRF binding (P = 0.0101);
MVP
0.37
MPC
0.052
ClinPred
0.88
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.50

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: rs745521985; hg19: chr12-16109941; COSMIC: COSV70773798; API