NM_003677.5:c.95T>G

Variant names:

• chr12-122753796-T-G
• rs376132191
• NM_003677.5:c.95T>G

Variant summary

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

The NM_003677.5(DENR):​c.95T>G​(p.Leu32Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. L32P) 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: 5.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENR	NM_003677.5	c.95T>G	p.Leu32Arg	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.95T>G	p.Leu32Arg	missense_variant	Exon 2 of 8	1	NM_003677.5	ENSP00000280557.6
DENR	ENST00000455982.2	c.95T>G	p.Leu32Arg	missense_variant	Exon 2 of 8	5		ENSP00000413661.2
DENR	ENST00000537955.1	n.208T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
DENR	ENST00000539463.1	n.228T>G		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		5.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.26
Sift	Benign	0.52	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.56	P;P
Vest4		0.92
MutPred		0.56		Gain of catalytic residue at C37 (P = 4e-04);Gain of catalytic residue at C37 (P = 4e-04);
MVP		0.53
MPC		1.5
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.67
gMVP		0.82
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs376132191; hg19: chr12-123238343;