5-6631974-G-C

Variant names:

• chr5-6631974-G-C
• NM_017755.6:c.258C>G

Variant summary

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

The NM_017755.6(NSUN2):​c.258C>G​(p.His86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,578 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: 0.0000014 (0 hom.)
• Consequence: NSUN2 NM_017755.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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 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	c.258C>G	p.His86Gln	missense_variant	Exon 3 of 19	ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.254+625C>G		intron_variant	Intron 2 of 17		NP_001180384.1
NSUN2	NR_037947.2	n.323C>G		non_coding_transcript_exon_variant	Exon 3 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.258C>G	p.His86Gln	missense_variant	Exon 3 of 19	1	NM_017755.6	ENSP00000264670.6
NSUN2	ENST00000506139.5	c.254+625C>G		intron_variant	Intron 2 of 17	2		ENSP00000420957.1
NSUN2	ENST00000504374.5	n.258C>G		non_coding_transcript_exon_variant	Exon 3 of 18	2		ENSP00000421783.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454578 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723882

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-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	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Benign	0.29	T
Sift4G	Benign	0.33	T
Polyphen		0.066	B
Vest4		0.86
MutPred		0.34		Loss of helix (P = 0.0237);
MVP		0.85
MPC		0.085
ClinPred		0.43	T
GERP RS		-8.6
Varity_R		0.17
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -1

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: chr5-6632087;