rs759216076
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_173500.4(TTBK2):c.1126C>T(p.Arg376Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R376H) has been classified as Uncertain significance.
Frequency
Consequence
NM_173500.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTBK2 | NM_173500.4 | c.1126C>T | p.Arg376Cys | missense_variant | 11/15 | ENST00000267890.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTBK2 | ENST00000267890.11 | c.1126C>T | p.Arg376Cys | missense_variant | 11/15 | 5 | NM_173500.4 | P1 | |
TTBK2 | ENST00000567840.5 | c.1126C>T | p.Arg376Cys | missense_variant | 11/12 | 1 | |||
TTBK2 | ENST00000567274.5 | c.1021C>T | p.Arg341Cys | missense_variant | 10/11 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249390Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135294
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727236
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2023 | The c.1126C>T (p.R376C) alteration is located in exon 11 (coding exon 10) of the TTBK2 gene. This alteration results from a C to T substitution at nucleotide position 1126, causing the arginine (R) at amino acid position 376 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 26, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at