Variant 12-15982325-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015954.4(DERA):c.526C>T(p.Arg176Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,460,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DERA
NM_015954.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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:

DERA (HGNC:):

DERA links:

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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=0.29415655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DERA	NM_015954.4 linkuse as main transcript	c.526C>T	p.Arg176Cys	missense_variant	6/9	ENST00000428559.7	NP_057038.2	Q9Y315
DERA	XM_024449001.2 linkuse as main transcript	c.262C>T	p.Arg88Cys	missense_variant	6/9		XP_024304769.1
DERA	NM_001300779.2 linkuse as main transcript	c.508+19378C>T		intron_variant			NP_001287708.1	E9PPM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DERA	ENST00000428559.7 linkuse as main transcript	c.526C>T	p.Arg176Cys	missense_variant	6/9	1	NM_015954.4	ENSP00000416583.2		Q9Y315

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248308

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134692

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000117

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:

0.0000137

AC:

AN:

1460840

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.526C>T (p.R176C) alteration is located in exon 6 (coding exon 6) of the DERA gene. This alteration results from a C to T substitution at nucleotide position 526, causing the arginine (R) at amino acid position 176 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

0.068

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;.;T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

L;.;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.0

D;D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.10

T;T;T;T;T

Sift4G

Benign

0.074

T;T;T;T;T

Polyphen

0.0020

B;.;.;.;.

Vest4

0.51

MutPred

0.61

Loss of catalytic residue at R176 (P = 0.0384);.;.;.;.;

MVP

0.49

MPC

0.051

ClinPred

0.37

GERP RS

3.2

Varity_R

0.33

gMVP

0.67

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