Variant 12-110614207-C-CTCCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_001082538.3(TCTN1):c.26_29dupTCCT(p.Val11ProfsTer72) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 in 1,425,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

TCTN1
NM_001082538.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.12

Variant links:

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]

TCTN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.983 CDS is truncated, and there are 1 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-110614207-C-CTCCT is Pathogenic according to our data. Variant chr12-110614207-C-CTCCT is described in ClinVar as [Pathogenic]. Clinvar id is 1033279.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN1	NM_001082538.3 link	c.26_29dupTCCT	p.Val11ProfsTer72	frameshift_variant	Exon 1 of 15	ENST00000397659.9	NP_001076007.1	Q2MV58-2B4DIB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCTN1	ENST00000397659.9 link	c.26_29dupTCCT	p.Val11ProfsTer72	frameshift_variant	Exon 1 of 15	1	NM_001082538.3	ENSP00000380779.4	Q2MV58-2
TCTN1	ENST00000551590.5 link	c.26_29dupTCCT	p.Val11ProfsTer72	frameshift_variant	Exon 1 of 15	1		ENSP00000448735.1	Q2MV58-1
TCTN1	ENST00000397655.7 link	c.26_29dupTCCT	p.Val11ProfsTer72	frameshift_variant	Exon 1 of 15	1		ENSP00000380775.3	Q2MV58-3
TCTN1	ENST00000397656.8 link	n.26_29dupTCCT		non_coding_transcript_exon_variant	Exon 1 of 16	2		ENSP00000380776.4	J3KPW2
TCTN1	ENST00000480648.5 link	n.26_29dupTCCT		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000437196.1	E9PNE4
TCTN1	ENST00000495659.6 link	n.26_29dupTCCT		non_coding_transcript_exon_variant	Exon 1 of 15	2		ENSP00000436673.2	E9PIB8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000534

AC:

AN:

187210

Hom.:

AF XY:

0.00000978

AC XY:

AN XY:

102278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000394

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000982

AC:

AN:

1425812

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

706030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000147

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Joubert syndrome 13

Pathogenic:1

Feb 01, 2018

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over