rs147152016
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005619.5(RTN2):c.385A>T(p.Thr129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005619.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.385A>T | p.Thr129Ser | missense_variant | 3/11 | ENST00000245923.9 | |
RTN2 | NM_206900.3 | c.385A>T | p.Thr129Ser | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.385A>T | p.Thr129Ser | missense_variant | 3/11 | 1 | NM_005619.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000987 AC: 15AN: 151946Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250542Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135546
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461208Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726936
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74334
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | ClinVar contains an entry for this variant (Variation ID: 582175). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with RTN2-related conditions. This variant is present in population databases (rs147152016, gnomAD 0.05%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 129 of the RTN2 protein (p.Thr129Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at