19-45488945-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000245923.9(RTN2):c.1283C>T(p.Thr428Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,611,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T428K) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000245923.9 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.1283C>T | p.Thr428Met | missense_variant | 7/11 | ENST00000245923.9 | NP_005610.1 | |
RTN2 | NM_206900.3 | c.1064C>T | p.Thr355Met | missense_variant | 6/10 | NP_996783.1 | ||
RTN2 | NM_206901.3 | c.263C>T | p.Thr88Met | missense_variant | 3/7 | NP_996784.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.1283C>T | p.Thr428Met | missense_variant | 7/11 | 1 | NM_005619.5 | ENSP00000245923 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 243378Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131636
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1459286Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 725658
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2023 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine 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 (rs74368484, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 428 of the RTN2 protein (p.Thr428Met). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at