chr5-6599827-C-T

Variant names:

• chr5-6599827-C-T
• rs3776448
• NM_017755.6:c.*99G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017755.6(NSUN2):​c.*99G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,032,074 control chromosomes in the GnomAD database, including 9,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1339 hom., cov: 33)
  • Exomes 𝑓: 0.13 (8495 hom.)
• Consequence: NSUN2 NM_017755.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0880
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-6599827-C-T is Benign according to our data. Variant chr5-6599827-C-T is described in ClinVar as Benign. ClinVar VariationId is 354043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	NM_017755.6	MANE Select	c.*99G>A		3_prime_UTR	Exon 19 of 19	NP_060225.4
	NSUN2	NM_001193455.2		c.*99G>A		3_prime_UTR	Exon 18 of 18	NP_001180384.1	Q08J23-2
	NSUN2	NR_037947.2		n.2383G>A		non_coding_transcript_exon	Exon 18 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	ENST00000264670.11	TSL:1 MANE Select	c.*99G>A		3_prime_UTR	Exon 19 of 19	ENSP00000264670.6	Q08J23-1
	NSUN2	ENST00000505892.5	TSL:1	n.2972G>A		non_coding_transcript_exon	Exon 13 of 13
	NSUN2	ENST00000902915.1		c.*99G>A		3_prime_UTR	Exon 20 of 20	ENSP00000572974.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17582 AN: 152176 Hom.: 1338 Cov.: 33

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.128 AC: 112602 AN: 879780 Hom.: 8495 Cov.: 12 AF XY: 0.128 AC XY: 57958 AN XY: 451638

African (AFR) AF: 0.0358 AC: 773 AN: 21608

American (AMR) AF: 0.225 AC: 7473 AN: 33186

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 1141 AN: 18000

East Asian (EAS) AF: 0.249 AC: 9201 AN: 36892

South Asian (SAS) AF: 0.166 AC: 10372 AN: 62558

European-Finnish (FIN) AF: 0.213 AC: 8057 AN: 37744

Middle Eastern (MID) AF: 0.0447 AC: 127 AN: 2840

European-Non Finnish (NFE) AF: 0.112 AC: 70419 AN: 626112

Other (OTH) AF: 0.123 AC: 5039 AN: 40840

GnomAD4 genome AF: 0.115 AC: 17586 AN: 152294 Hom.: 1339 Cov.: 33 AF XY: 0.124 AC XY: 9201 AN XY: 74458

African (AFR) AF: 0.0406 AC: 1688 AN: 41590

American (AMR) AF: 0.181 AC: 2773 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3472

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5172

South Asian (SAS) AF: 0.163 AC: 786 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2449 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8038 AN: 68024

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.111 Hom.: 1125

Bravo AF: 0.110

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual disability, autosomal recessive 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		-0.088
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs3776448; hg19: chr5-6599940; COSMIC: COSV52953689; COSMIC: COSV52953689;