12-110645031-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001082538.3(TCTN1):c.1396G>T(p.Gly466Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0232 in 1,614,174 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001082538.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCTN1 | ENST00000397659.9 | c.1396G>T | p.Gly466Cys | missense_variant | Exon 12 of 15 | 1 | NM_001082538.3 | ENSP00000380779.4 | ||
TCTN1 | ENST00000551590.5 | c.1396G>T | p.Gly466Cys | missense_variant | Exon 12 of 15 | 1 | ENSP00000448735.1 | |||
TCTN1 | ENST00000397655.7 | c.1354G>T | p.Gly452Cys | missense_variant | Exon 12 of 15 | 1 | ENSP00000380775.3 | |||
TCTN1 | ENST00000397656.8 | n.*1029G>T | non_coding_transcript_exon_variant | Exon 13 of 16 | 2 | ENSP00000380776.4 | ||||
TCTN1 | ENST00000480648.5 | n.*672G>T | non_coding_transcript_exon_variant | Exon 13 of 16 | 5 | ENSP00000437196.1 | ||||
TCTN1 | ENST00000495659.6 | n.*1154G>T | non_coding_transcript_exon_variant | Exon 12 of 15 | 2 | ENSP00000436673.2 | ||||
TCTN1 | ENST00000397656.8 | n.*1029G>T | 3_prime_UTR_variant | Exon 13 of 16 | 2 | ENSP00000380776.4 | ||||
TCTN1 | ENST00000480648.5 | n.*672G>T | 3_prime_UTR_variant | Exon 13 of 16 | 5 | ENSP00000437196.1 | ||||
TCTN1 | ENST00000495659.6 | n.*1154G>T | 3_prime_UTR_variant | Exon 12 of 15 | 2 | ENSP00000436673.2 |
Frequencies
GnomAD3 genomes AF: 0.0166 AC: 2532AN: 152174Hom.: 36 Cov.: 32
GnomAD3 exomes AF: 0.0214 AC: 5338AN: 249560Hom.: 106 AF XY: 0.0228 AC XY: 3086AN XY: 135398
GnomAD4 exome AF: 0.0239 AC: 34883AN: 1461882Hom.: 542 Cov.: 30 AF XY: 0.0244 AC XY: 17762AN XY: 727242
GnomAD4 genome AF: 0.0166 AC: 2535AN: 152292Hom.: 37 Cov.: 32 AF XY: 0.0176 AC XY: 1310AN XY: 74468
ClinVar
Submissions by phenotype
not specified Benign:3
- -
- -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
- -
not provided Benign:1
- -
Joubert syndrome 13 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at