5-6599950-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_017755.6(NSUN2):c.2280G>A(p.Pro760=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,592 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
NSUN2
NM_017755.6 synonymous
NM_017755.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.86
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 5-6599950-C-T is Benign according to our data. Variant chr5-6599950-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 750687.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-4.86 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NSUN2 | NM_017755.6 | c.2280G>A | p.Pro760= | synonymous_variant | 19/19 | ENST00000264670.11 | NP_060225.4 | |
NSUN2 | NM_001193455.2 | c.2175G>A | p.Pro725= | synonymous_variant | 18/18 | NP_001180384.1 | ||
NSUN2 | NR_037947.2 | n.2260G>A | non_coding_transcript_exon_variant | 18/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NSUN2 | ENST00000264670.11 | c.2280G>A | p.Pro760= | synonymous_variant | 19/19 | 1 | NM_017755.6 | ENSP00000264670 | P2 | |
LINC01018 | ENST00000661215.1 | n.757-171C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251246Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135782
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461342Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726954
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 27, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at