chr5-6599930-C-A

Variant names:

• chr5-6599930-C-A
• rs140673211
• NM_017755.6:c.2300G>T

Variant summary

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

The NM_017755.6(NSUN2):​c.2300G>T​(p.Arg767Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R767Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NSUN2 NM_017755.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770
• Publications: 4 publications found

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)

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=0.14090016).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017755.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	NM_017755.6	MANE Select	c.2300G>T	p.Arg767Leu	missense	Exon 19 of 19	NP_060225.4
	NSUN2	NM_001193455.2		c.2195G>T	p.Arg732Leu	missense	Exon 18 of 18	NP_001180384.1
	NSUN2	NR_037947.2		n.2280G>T		non_coding_transcript_exon	Exon 18 of 18

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	ENST00000264670.11	TSL:1 MANE Select	c.2300G>T	p.Arg767Leu	missense	Exon 19 of 19	ENSP00000264670.6
	NSUN2	ENST00000505892.5	TSL:1	n.2869G>T		non_coding_transcript_exon	Exon 13 of 13
	NSUN2	ENST00000902915.1		c.2324G>T	p.Arg775Leu	missense	Exon 20 of 20	ENSP00000572974.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.77
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.33	B
Vest4		0.29
MutPred		0.22		Gain of stability (P = 0.0098)
MVP		0.26
MPC		0.095
ClinPred		0.52	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.30
Mutation Taster		=99/1	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

dbSNP: rs140673211; hg19: chr5-6600043;