rs199959678

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The NM_017755.6(NSUN2):​c.97-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NSUN2
NM_017755.6 intron

Scores

2
Splicing: ADA: 0.0001236
2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.505
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 5-6632766-G-A is Benign according to our data. Variant chr5-6632766-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211763.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000249 (38/152314) while in subpopulation AMR AF= 0.00235 (36/15306). AF 95% confidence interval is 0.00175. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NSUN2NM_017755.6 linkc.97-10C>T intron_variant Intron 1 of 18 ENST00000264670.11 NP_060225.4 Q08J23-1
NSUN2NM_001193455.2 linkc.97-10C>T intron_variant Intron 1 of 17 NP_001180384.1 Q08J23-2
NSUN2NR_037947.2 linkn.162-10C>T intron_variant Intron 1 of 17

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NSUN2ENST00000264670.11 linkc.97-10C>T intron_variant Intron 1 of 18 1 NM_017755.6 ENSP00000264670.6 Q08J23-1
NSUN2ENST00000506139.5 linkc.97-10C>T intron_variant Intron 1 of 17 2 ENSP00000420957.1 Q08J23-2
NSUN2ENST00000504374.5 linkn.97-10C>T intron_variant Intron 1 of 17 2 ENSP00000421783.1 A0A140T9Y7

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000647
AC:
16
AN:
247282
Hom.:
0
AF XY:
0.0000523
AC XY:
7
AN XY:
133822
show subpopulations
Gnomad AFR exome
AF:
0.0000623
Gnomad AMR exome
AF:
0.000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.000332
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1460048
Hom.:
0
Cov.:
36
AF XY:
0.0000193
AC XY:
14
AN XY:
726176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000270
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000249
AC:
38
AN:
152314
Hom.:
0
Cov.:
33
AF XY:
0.000295
AC XY:
22
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000298

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 17, 2014- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
7.8
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00012
dbscSNV1_RF
Benign
0.0060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199959678; hg19: chr5-6632879; API