rs144543830
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_015631.6(TCTN3):c.1425G>A(p.Arg475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,613,958 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 0 hom. )
Consequence
TCTN3
NM_015631.6 synonymous
NM_015631.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.444
Genes affected
TCTN3 (HGNC:24519): (tectonic family member 3) This gene encodes a member of the tectonic gene family which functions in Hedgehog signal transduction and development of the neural tube. Mutations in this gene have been associated with Orofaciodigital Syndrome IV and Joubert Syndrom 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 10-95682678-C-T is Benign according to our data. Variant chr10-95682678-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 383719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-95682678-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.444 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000458 (669/1461706) while in subpopulation MID AF= 0.00225 (13/5766). AF 95% confidence interval is 0.00133. There are 0 homozygotes in gnomad4_exome. There are 348 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCTN3 | NM_015631.6 | c.1425G>A | p.Arg475= | synonymous_variant | 12/14 | ENST00000371217.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCTN3 | ENST00000371217.10 | c.1425G>A | p.Arg475= | synonymous_variant | 12/14 | 1 | NM_015631.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152134Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000597 AC: 150AN: 251214Hom.: 0 AF XY: 0.000655 AC XY: 89AN XY: 135780
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GnomAD4 exome AF: 0.000458 AC: 669AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.000479 AC XY: 348AN XY: 727156
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GnomAD4 genome ? AF: 0.000617 AC: 94AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 49AN XY: 74432
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 15, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | TCTN3: BP4, BP7 - |
Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at