rs992264498

Variant names:

• chr12-15956971-C-G
• rs992264498
• NM_015954.4:c.67C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-15956971-C-G
• chr12-15956971-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015954.4(DERA):​c.67C>G​(p.Pro23Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P23S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DERA NM_015954.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1305291).

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.67C>G	p.Pro23Ala	missense	Exon 2 of 9	NP_057038.2	Q9Y315
	DERA	NM_001300779.2		c.67C>G	p.Pro23Ala	missense	Exon 2 of 8	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.67C>G	p.Pro23Ala	missense	Exon 2 of 9	ENSP00000416583.2	Q9Y315
	DERA	ENST00000526530.1	TSL:1	c.-198C>G		5_prime_UTR	Exon 2 of 9	ENSP00000431757.1	G3V158
	DERA	ENST00000885123.1		c.67C>G	p.Pro23Ala	missense	Exon 2 of 9	ENSP00000555182.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.060
Sift	Benign	0.27	T
Sift4G	Benign	0.66	T
Polyphen		0.0010	B
Vest4		0.41
MutPred		0.36		Loss of loop (P = 9e-04)
MVP		0.38
MPC		0.041
ClinPred		0.57	D
GERP RS		4.2
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.032
gMVP		0.31
Mutation Taster		=72/28	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: rs992264498; hg19: chr12-16109905;