Genetic Variant NM_017755.6:c.763G>C (chr5-6620158-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017755.6(NSUN2):c.763G>C(p.Gly255Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,956 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NSUN2
NM_017755.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.65

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]

NSUN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
NSUN2	NM_017755.6 link	c.763G>C	p.Gly255Arg	missense_variant	Exon 7 of 19	ENST00000264670.11	NP_060225.4	Q08J23-1
NSUN2	NM_001193455.2 link	c.658G>C	p.Gly220Arg	missense_variant	Exon 6 of 18		NP_001180384.1	Q08J23-2
NSUN2	NR_037947.2 link	n.743G>C		non_coding_transcript_exon_variant	Exon 6 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11 link	c.763G>C	p.Gly255Arg	missense_variant	Exon 7 of 19	1	NM_017755.6	ENSP00000264670.6		Q08J23-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457956

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725290

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.6

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;.

Vest4

0.60

MutPred

0.58

Gain of methylation at K257 (P = 0.0504);.;

MVP

0.66

MPC

1.9

ClinPred

1.0

GERP RS

6.0

Varity_R

0.57

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over