chr5-6613714-T-C

Position:

• chr5-6613714-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
NSUN2	NM_017755.6	c.1022-1916A>G		intron_variant		ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.917-1916A>G		intron_variant			NP_001180384.1
NSUN2	NR_037947.2	n.1002-1916A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.1022-1916A>G		intron_variant		1	NM_017755.6	ENSP00000264670.6
NSUN2	ENST00000505892.5	n.1591-1916A>G		intron_variant		1
NSUN2	ENST00000506139.5	c.917-1916A>G		intron_variant		2		ENSP00000420957.1
NSUN2	ENST00000504374.5	n.*328-1916A>G		intron_variant		2		ENSP00000421783.1

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

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.671

Alfa AF: 0.672 Hom.: 31879

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

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

LitVar

Other links and lift over

dbSNP: rs4701742; hg19: chr5-6613827;