rs767886169
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBS1_Supporting
The NM_002361.4(MAG):c.1646C>T(p.Ser549Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S549S) has been classified as Benign.
Frequency
Consequence
NM_002361.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAG | NM_002361.4 | c.1646C>T | p.Ser549Leu | missense_variant | 10/11 | ENST00000392213.8 | |
MAG | NM_001199216.2 | c.1571C>T | p.Ser524Leu | missense_variant | 10/11 | ||
MAG | NM_080600.3 | c.1646C>T | p.Ser549Leu | missense_variant | 10/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAG | ENST00000392213.8 | c.1646C>T | p.Ser549Leu | missense_variant | 10/11 | 1 | NM_002361.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248584Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134478
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460836Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726668
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 75 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 03, 2019 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has been observed in the heterozygous state in an individual affected with hereditary spastic paraplegia (HSP) (PMID: 28832565). ClinVar contains an entry for this variant (Variation ID: 424680). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces serine with leucine at codon 549 of the MAG protein (p.Ser549Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde | Mar 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at