NM_015954.4:c.526C>T

Variant names:

• chr12-15982325-C-T
• rs757878771
• NM_015954.4:c.526C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29415655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015954.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DERA	NM_015954.4	MANE Select	c.526C>T	p.Arg176Cys	missense	Exon 6 of 9	NP_057038.2	Q9Y315
	DERA	NM_001300779.2		c.508+19378C>T		intron	N/A	NP_001287708.1	E9PPM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DERA	ENST00000428559.7	TSL:1 MANE Select	c.526C>T	p.Arg176Cys	missense	Exon 6 of 9	ENSP00000416583.2	Q9Y315
	DERA	ENST00000526530.1	TSL:1	c.262C>T	p.Arg88Cys	missense	Exon 6 of 9	ENSP00000431757.1	G3V158
	DERA	ENST00000885123.1		c.526C>T	p.Arg176Cys	missense	Exon 6 of 9	ENSP00000555182.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000282 AC: 7 AN: 248308 AF XY: 0.0000223

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1460840 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726654

African (AFR) AF: 0.0000299 AC: 1 AN: 33426

American (AMR) AF: 0.000112 AC: 5 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111650

Other (OTH) AF: 0.0000331 AC: 2 AN: 60338

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.17
Sift	Benign	0.10	T
Sift4G	Benign	0.074	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	T
GERP RS		3.2
Varity_R		0.33
gMVP		0.67
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs757878771; hg19: chr12-16135259; COSMIC: COSV70774176; COSMIC: COSV70774176;