NM_017970.4:c.3451G>T

Variant names:

• chr14-90278380-C-A
• NM_017970.4:c.3451G>T

Variant summary

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

The NM_017970.4(NRDE2):​c.3451G>T​(p.Val1151Leu) 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. 14/22 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)
• Consequence: NRDE2 NM_017970.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

Genes affected

NRDE2 (HGNC:20186): (NRDE-2, necessary for RNA interference, domain containing) Involved in several processes, including RNA splicing; negative regulation of RNA catabolic process; and positive regulation of RNA export from nucleus. Located in nuclear speck and nucleolus. [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=0.22172683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017970.4. 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
	NRDE2	NM_017970.4	MANE Select	c.3451G>T	p.Val1151Leu	missense	Exon 14 of 14	NP_060440.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDE2	ENST00000354366.8	TSL:1 MANE Select	c.3451G>T	p.Val1151Leu	missense	Exon 14 of 14	ENSP00000346335.3	Q9H7Z3
	NRDE2	ENST00000553409.5	TSL:1	n.*2976G>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000451025.1	G3V338
	NRDE2	ENST00000556189.5	TSL:1	n.*1929G>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000452107.1	H0YJT6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.22
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Benign	0.24	T
Polyphen		0.60	P
Vest4		0.17
MutPred		0.35		Gain of catalytic residue at V1151 (P = 0.0064)
MVP		0.42
MPC		0.064
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.27
Mutation Taster		=73/27	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

hg19: chr14-90744724;