Genetic Variant DERA:c.-162C>T (chr12-15957007-C-T) – ACMG Classification: Uncertain_significance (1 pts)

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

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]

DERA links:

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
DERA	NM_015954.4 link	c.103C>T	p.Arg35Cys	missense_variant	Exon 2 of 9	ENST00000428559.7	NP_057038.2	Q9Y315
DERA	XM_024449001.2 link	c.-162C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9		XP_024304769.1
DERA	NM_001300779.2 link	c.103C>T	p.Arg35Cys	missense_variant	Exon 2 of 8		NP_001287708.1	E9PPM8
DERA	XM_024449001.2 link	c.-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
DERA	ENST00000428559.7 link	c.103C>T	p.Arg35Cys	missense_variant	Exon 2 of 9	1	NM_015954.4	ENSP00000416583.2		Q9Y315

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249080

Hom.:

AF XY:

0.0000148

AC XY:

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:

AN:

1461636

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

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.:

Alfa

AF:

0.0000555

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000828

AC:

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

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

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

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.7

M;.;.

PrimateAI

Benign

0.47

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over