rs142353672
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_017986.4(SLC52A1):c.1240G>A(p.Ala414Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,578 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 (★).
Frequency
Consequence
NM_017986.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A1 | NM_017986.4 | c.1240G>A | p.Ala414Thr | missense_variant | 5/5 | ENST00000254853.10 | |
LOC105371501 | XR_002958101.2 | n.339+1395C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A1 | ENST00000254853.10 | c.1240G>A | p.Ala414Thr | missense_variant | 5/5 | 1 | NM_017986.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000759 AC: 19AN: 250406Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135336
GnomAD4 exome AF: 0.000157 AC: 230AN: 1461396Hom.: 0 Cov.: 32 AF XY: 0.000173 AC XY: 126AN XY: 727008
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74344
ClinVar
Submissions by phenotype
Ariboflavinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 583054). This missense change has been observed in individual(s) with sporadic early onset Parkinson disease (PMID: 23506902). This variant is present in population databases (rs142353672, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 414 of the SLC52A1 protein (p.Ala414Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at