rs780915320

Variant names:

• chr12-122753763-C-G
• rs780915320
• NM_003677.5:c.62C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-122753763-C-G
• chr12-122753763-C-T

Variant summary

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

The NM_003677.5(DENR):​c.62C>G​(p.Ala21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. A21V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DENR NM_003677.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 0 publications found

Genes affected

DENR (HGNC:2769): (density regulated re-initiation and release factor) This gene encodes a protein whose expression was found to increase in cultured cells at high density but not during growth arrest. This gene was also shown to have increased expression in cells overexpressing HER-2/neu proto-oncogene. The protein contains an SUI1 domain. In budding yeast, SUI1 is a translation initiation factor that along with eIF-2 and the initiator tRNA-Met, directs the ribosome to the proper translation start site. Proteins similar to SUI have been found in mammals, insects, and plants. [provided by RefSeq, Jul 2008]

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=0.10415548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENR	NM_003677.5	c.62C>G	p.Ala21Gly	missense_variant	Exon 2 of 8	ENST00000280557.11	NP_003668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENR	ENST00000280557.11	c.62C>G	p.Ala21Gly	missense_variant	Exon 2 of 8	1	NM_003677.5	ENSP00000280557.6
DENR	ENST00000455982.2	c.62C>G	p.Ala21Gly	missense_variant	Exon 2 of 8	5		ENSP00000413661.2
DENR	ENST00000537955.1	n.175C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
DENR	ENST00000539463.1	n.195C>G		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		3.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.038
Sift	Uncertain	0.020	D;T
Sift4G	Benign	0.24	T;T
Polyphen		0.017	B;B
Vest4		0.19
MutPred		0.26		Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);
MVP		0.39
MPC		0.54
ClinPred		0.61	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.22
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs780915320; hg19: chr12-123238310;