5-6604163-C-G

Variant names:

• chr5-6604163-C-G
• NM_017755.6:c.1932G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017755.6(NSUN2):​c.1932G>C​(p.Glu644Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NSUN2 NM_017755.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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]

ACMG classification

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=0.10377556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSUN2	NM_017755.6	c.1932G>C	p.Glu644Asp	missense_variant	Exon 17 of 19	ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.1827G>C	p.Glu609Asp	missense_variant	Exon 16 of 18		NP_001180384.1
NSUN2	NR_037947.2	n.1912G>C		non_coding_transcript_exon_variant	Exon 16 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.1932G>C	p.Glu644Asp	missense_variant	Exon 17 of 19	1	NM_017755.6	ENSP00000264670.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.084	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.085
Sift	Benign	0.11	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.014	B;.
Vest4		0.12
MutPred		0.41		Gain of helix (P = 0.132);.;
MVP		0.53
MPC		0.049
ClinPred		0.15	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.079
gMVP		0.51

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: chr5-6604276;