chr5-6599379-TG-T

Position:

• chr5-6599379-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017755.6(NSUN2):​c.*546del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 152,842 control chromosomes in the GnomAD database, including 147 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (147 hom., cov: 32)
  • Exomes 𝑓: 0.040 (0 hom.)
• Consequence: NSUN2 NM_017755.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.834

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-6599379-TG-T is Benign according to our data. Variant chr5-6599379-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 354040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSUN2	NM_017755.6	c.*546del		3_prime_UTR_variant	19/19	ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.*546del		3_prime_UTR_variant	18/18		NP_001180384.1
NSUN2	NR_037947.2	n.2830del		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.*546del		3_prime_UTR_variant	19/19	1	NM_017755.6	ENSP00000264670	P2
LINC01018	ENST00000661215.1	n.757-739del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6021 AN: 152148 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0369

GnomAD4 exome AF: 0.0399 AC: 23 AN: 576 Hom.: 0 Cov.: 0 AF XY: 0.0460 AC XY: 16 AN XY: 348

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0370

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0395 AC: 6022 AN: 152266 Hom.: 147 Cov.: 32 AF XY: 0.0385 AC XY: 2868 AN XY: 74452

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0354

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0471 Hom.: 31

Bravo AF: 0.0390

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs200230801; hg19: chr5-6599492;