5-6599948-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017755.6(NSUN2):​c.2282C>A​(p.Ala761Glu) 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. 15/21 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

NSUN2
NM_017755.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.203
Variant links:
Genes affected
NSUN2 (HGNC:25994): (NOP2/Sun RNA methyltransferase 2) This gene encodes a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2011]
LINC01018 (HGNC:27394): (long intergenic non-protein coding RNA 1018)

Genome browser will be placed here

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=0.075900674).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NSUN2NM_017755.6 linkc.2282C>A p.Ala761Glu missense_variant Exon 19 of 19 ENST00000264670.11 NP_060225.4 Q08J23-1
NSUN2NM_001193455.2 linkc.2177C>A p.Ala726Glu missense_variant Exon 18 of 18 NP_001180384.1 Q08J23-2
NSUN2NR_037947.2 linkn.2262C>A non_coding_transcript_exon_variant Exon 18 of 18

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NSUN2ENST00000264670.11 linkc.2282C>A p.Ala761Glu missense_variant Exon 19 of 19 1 NM_017755.6 ENSP00000264670.6 Q08J23-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 27, 2016
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.A761E variant (also known as c.2282C>A), located in coding exon 19 of the NSUN2 gene, results from a C to A substitution at nucleotide position 2282. The alanine at codon 761 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
8.6
DANN
Benign
0.82
DEOGEN2
Benign
0.037
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.50
T;T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.33
N;N
REVEL
Benign
0.015
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.028
D;D
Polyphen
0.017
B;.
Vest4
0.13
MutPred
0.28
Gain of solvent accessibility (P = 9e-04);.;
MVP
0.23
MPC
0.10
ClinPred
0.084
T
GERP RS
-1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.054
gMVP
0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375624381; hg19: chr5-6600061; API