12-110628746-ACT-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_001082538.3(TCTN1):c.473-20_473-19delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,569,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

TCTN1
NM_001082538.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.982

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:

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]

HVCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 12-110628746-ACT-A is Benign according to our data. Variant chr12-110628746-ACT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 449853.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN1	NM_001082538.3 link	c.473-20_473-19delCT		intron_variant	Intron 3 of 14	ENST00000397659.9	NP_001076007.1	Q2MV58-2B4DIB9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCTN1	ENST00000397659.9 link	c.473-20_473-19delCT	intron_variant	Intron 3 of 14	1	NM_001082538.3	ENSP00000380779.4	Q2MV58-2
TCTN1	ENST00000551590.5 link	c.473-20_473-19delCT	intron_variant	Intron 3 of 14	1		ENSP00000448735.1	Q2MV58-1
TCTN1	ENST00000397655.7 link	c.473-20_473-19delCT	intron_variant	Intron 3 of 14	1		ENSP00000380775.3	Q2MV58-3
TCTN1	ENST00000397656.8 link	n.106-20_106-19delCT	intron_variant	Intron 4 of 15	2		ENSP00000380776.4	J3KPW2
TCTN1	ENST00000480648.5 link	n.473-20_473-19delCT	intron_variant	Intron 3 of 15	5		ENSP00000437196.1	E9PNE4
TCTN1	ENST00000495659.6 link	n.231-20_231-19delCT	intron_variant	Intron 3 of 14	2		ENSP00000436673.2	E9PIB8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000422

AC:

AN:

237088

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129410

show subpopulations

Gnomad AFR exome

AF:

0.0000668

Gnomad AMR exome

AF:

0.0000908

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.0000367

AC:

AN:

1417092

Hom.:

AF XY:

0.0000339

AC XY:

AN XY:

707338

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000390

Gnomad4 OTH exome

AF:

0.0000679

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 24, 2017

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A variant of uncertain significance has been identified in the TCTN1 gene. The c.473-20_473-19delCT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.473-20_473-19delCT variant is observed in 1/7002 (0.01%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice prediction models predict that c.473-20_473-19delCT damages or destroys the natural splice acceptor site of intron 20, which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

May 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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