5-6613714-T-C

Variant names:

• chr5-6613714-T-C
• rs4701742
• NM_017755.6:c.1022-1916A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017755.6(NSUN2):​c.1022-1916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,014 control chromosomes in the GnomAD database, including 32,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (32944 hom., cov: 32)
• Consequence: NSUN2 NM_017755.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSUN2	NM_017755.6	c.1022-1916A>G		intron_variant	Intron 9 of 18	ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.917-1916A>G		intron_variant	Intron 8 of 17		NP_001180384.1
NSUN2	NR_037947.2	n.1002-1916A>G		intron_variant	Intron 8 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.1022-1916A>G		intron_variant	Intron 9 of 18	1	NM_017755.6	ENSP00000264670.6

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99830 AN: 151892 Hom.: 32918 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.657 AC: 99903 AN: 152014 Hom.: 32944 Cov.: 32 AF XY: 0.649 AC XY: 48184 AN XY: 74296

African (AFR) AF: 0.655 AC: 27129 AN: 41436

American (AMR) AF: 0.616 AC: 9413 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2483 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3342 AN: 5164

South Asian (SAS) AF: 0.651 AC: 3135 AN: 4812

European-Finnish (FIN) AF: 0.551 AC: 5821 AN: 10560

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46253 AN: 67970

Other (OTH) AF: 0.671 AC: 1414 AN: 2106

Alfa AF: 0.671 Hom.: 42098

Bravo AF: 0.662

Asia WGS AF: 0.586 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4701742; hg19: chr5-6613827;