Variant 12-16036353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015954.4(DERA):c.872G>A(p.Ser291Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DERA
NM_015954.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.61

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.92

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DERA	NM_015954.4 linkuse as main transcript	c.872G>A	p.Ser291Asn	missense_variant	8/9	ENST00000428559.7	NP_057038.2	Q9Y315
DERA	NM_001300779.2 linkuse as main transcript	c.743G>A	p.Ser248Asn	missense_variant	7/8		NP_001287708.1	E9PPM8
DERA	XM_024449001.2 linkuse as main transcript	c.608G>A	p.Ser203Asn	missense_variant	8/9		XP_024304769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DERA	ENST00000428559.7 linkuse as main transcript	c.872G>A	p.Ser291Asn	missense_variant	8/9	1	NM_015954.4	ENSP00000416583.2		Q9Y315

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246524

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 07, 2023

The c.872G>A (p.S291N) alteration is located in exon 8 (coding exon 8) of the DERA gene. This alteration results from a G to A substitution at nucleotide position 872, causing the serine (S) at amino acid position 291 to be replaced by an asparagine (N). 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

Pathogenic

0.96

BayesDel_addAF

Benign

0.0068

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;D;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Pathogenic

0.88

MutationAssessor

Pathogenic

4.9

H;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

D;D;T

Sift4G

Benign

0.069

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.97

MutPred

0.71

Gain of sheet (P = 0.0073);.;.;

MVP

0.75

MPC

0.29

ClinPred

1.0

GERP RS

5.3

Varity_R

0.79

gMVP

0.98

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