12-110628749-GT-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_001082538.3(TCTN1):c.473-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,580,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
TCTN1
NM_001082538.3 splice_polypyrimidine_tract, intron
NM_001082538.3 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.239
Genes affected
TCTN1 (HGNC:26113): (tectonic family member 1) This gene encodes a member of a family of secreted and transmembrane proteins. The orthologous gene in mouse functions downstream of smoothened and rab23 to modulate hedgehog signal transduction. This protein is a component of the tectonic-like complex, which forms a barrier between the ciliary axoneme and the basal body. A mutation in this gene was found in a family with Joubert syndrome-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
HVCN1 (HGNC:28240): (hydrogen voltage gated channel 1) This gene encodes a voltage-gated protein channel protein expressed more highly in certain cells of the immune system. Phagocytic cells produce superoxide anions which require this channel protein, and in B cells this same process facilitates antibody production. This same channel protein, however, can also regulate functions in other cells including spermatozoa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 12-110628749-GT-G is Benign according to our data. Variant chr12-110628749-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1608758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCTN1 | NM_001082538.3 | c.473-10del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000397659.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCTN1 | ENST00000397659.9 | c.473-10del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001082538.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151704Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000427 AC: 10AN: 234146Hom.: 0 AF XY: 0.0000548 AC XY: 7AN XY: 127700
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GnomAD4 exome AF: 0.0000140 AC: 20AN: 1428180Hom.: 0 Cov.: 29 AF XY: 0.0000168 AC XY: 12AN XY: 712254
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GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151820Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74214
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 31, 2023 | - - |
TCTN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 31, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at