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GeneBe

14-90278380-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 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)

Consequence

NRDE2
NM_017970.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22172683).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NRDE2NM_017970.4 linkuse as main transcriptc.3451G>T p.Val1151Leu missense_variant 14/14 ENST00000354366.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NRDE2ENST00000354366.8 linkuse as main transcriptc.3451G>T p.Val1151Leu missense_variant 14/141 NM_017970.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 15, 2023The c.3451G>T (p.V1151L) alteration is located in exon 14 (coding exon 14) of the NRDE2 gene. This alteration results from a G to T substitution at nucleotide position 3451, causing the valine (V) at amino acid position 1151 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster
Benign
1.0
D;D
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-90744724; API