19-45488913-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The ENST00000245923.9(RTN2):c.1315G>A(p.Val439Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,609,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000245923.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.1315G>A | p.Val439Met | missense_variant | 7/11 | ENST00000245923.9 | NP_005610.1 | |
RTN2 | NM_206900.3 | c.1096G>A | p.Val366Met | missense_variant | 6/10 | NP_996783.1 | ||
RTN2 | NM_206901.3 | c.295G>A | p.Val99Met | missense_variant | 3/7 | NP_996784.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.1315G>A | p.Val439Met | missense_variant | 7/11 | 1 | NM_005619.5 | ENSP00000245923 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000167 AC: 4AN: 240216Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129870
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1457404Hom.: 0 Cov.: 33 AF XY: 0.0000262 AC XY: 19AN XY: 724506
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74488
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 13, 2024 | Variant summary: RTN2 c.1315G>A (p.Val439Met) results in a conservative amino acid change located in the Reticulon domain (IPR003388) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 348820 control chromosomes, predominantly at a frequency of 0.0012 in the Japanese subpopulation (gnomAD, jMorp (Tadaka_2024)). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance, however is not suggestive of a variant associated with autosomal dominant disease. To our knowledge, no occurrence of c.1315G>A in individuals affected with Spastic Paragplegia 12 and no experimental evidence demonstrating its impact on protein function have been reported. The following publication was ascertained in the context of this evaluation (PMID: 37930845). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at