rs144424516
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_013254.4(TBK1):c.1522C>A(p.Leu508Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000382 in 1,612,610 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_013254.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBK1 | NM_013254.4 | c.1522C>A | p.Leu508Ile | missense_variant, splice_region_variant | 14/21 | ENST00000331710.10 | |
TBK1 | XM_005268809.2 | c.1522C>A | p.Leu508Ile | missense_variant, splice_region_variant | 14/21 | ||
TBK1 | XM_005268810.2 | c.1522C>A | p.Leu508Ile | missense_variant, splice_region_variant | 14/21 | ||
TBK1 | XR_007063071.1 | n.1621C>A | splice_region_variant, non_coding_transcript_exon_variant | 14/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBK1 | ENST00000331710.10 | c.1522C>A | p.Leu508Ile | missense_variant, splice_region_variant | 14/21 | 1 | NM_013254.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00222 AC: 338AN: 152184Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000602 AC: 150AN: 249088Hom.: 3 AF XY: 0.000446 AC XY: 60AN XY: 134602
GnomAD4 exome AF: 0.000191 AC: 279AN: 1460308Hom.: 2 Cov.: 31 AF XY: 0.000164 AC XY: 119AN XY: 726426
GnomAD4 genome ? AF: 0.00221 AC: 337AN: 152302Hom.: 2 Cov.: 32 AF XY: 0.00208 AC XY: 155AN XY: 74476
ClinVar
Submissions by phenotype
TBK1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 25, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at