12-110645031-G-T

Variant names:

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

Genomes: 𝑓 0.017 ( 37 hom., cov: 32)

Exomes 𝑓: 0.024 ( 542 hom. )

Consequence

TCTN1
NM_001082538.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.63

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045828223).

BP6

Variant 12-110645031-G-T is Benign according to our data. Variant chr12-110645031-G-T is described in ClinVar as [Benign]. Clinvar id is 160095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110645031-G-T is described in Lovd as [Benign]. Variant chr12-110645031-G-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN1	NM_001082538.3 link	c.1396G>T	p.Gly466Cys	missense_variant	Exon 12 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.1396G>T	p.Gly466Cys	missense_variant	Exon 12 of 15	1	NM_001082538.3	ENSP00000380779.4	Q2MV58-2
TCTN1	ENST00000551590.5 link	c.1396G>T	p.Gly466Cys	missense_variant	Exon 12 of 15	1		ENSP00000448735.1	Q2MV58-1
TCTN1	ENST00000397655.7 link	c.1354G>T	p.Gly452Cys	missense_variant	Exon 12 of 15	1		ENSP00000380775.3	Q2MV58-3
TCTN1	ENST00000397656.8 link	n.*1029G>T		non_coding_transcript_exon_variant	Exon 13 of 16	2		ENSP00000380776.4	J3KPW2
TCTN1	ENST00000480648.5 link	n.*672G>T		non_coding_transcript_exon_variant	Exon 13 of 16	5		ENSP00000437196.1	E9PNE4
TCTN1	ENST00000495659.6 link	n.*1154G>T		non_coding_transcript_exon_variant	Exon 12 of 15	2		ENSP00000436673.2	E9PIB8
TCTN1	ENST00000397656.8 link	n.*1029G>T		3_prime_UTR_variant	Exon 13 of 16	2		ENSP00000380776.4	J3KPW2
TCTN1	ENST00000480648.5 link	n.*672G>T		3_prime_UTR_variant	Exon 13 of 16	5		ENSP00000437196.1	E9PNE4
TCTN1	ENST00000495659.6 link	n.*1154G>T		3_prime_UTR_variant	Exon 12 of 15	2		ENSP00000436673.2	E9PIB8

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2532

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00401

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0146

Gnomad SAS

AF:

0.0569

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.0214

AC:

5338

AN:

249560

Hom.:

106

AF XY:

0.0228

AC XY:

3086

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00368

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0118

Gnomad SAS exome

AF:

0.0522

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0230

Gnomad OTH exome

AF:

0.0195

GnomAD4 exome

AF:

0.0239

AC:

34883

AN:

1461882

Hom.:

542

Cov.:

AF XY:

0.0244

AC XY:

17762

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00370

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.0505

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.0247

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0166

AC:

2535

AN:

152292

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1310

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00399

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.0565

Gnomad4 FIN

AF:

0.00867

Gnomad4 NFE

AF:

0.0236

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0161

TwinsUK

AF:

0.0272

AC:

101

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.00397

AC:

ESP6500EA

AF:

0.0211

AC:

173

ExAC

AF:

0.0229

AC:

2769

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

EpiCase

AF:

0.0187

EpiControl

AF:

0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Joubert syndrome 13

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Meckel-Gruber syndrome;C0431399:Joubert syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T;.;.;.

Eigen

Benign

-0.023

Eigen_PC

Benign

0.0073

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.2

.;M;.;M;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.0

.;D;D;D;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.014

.;D;D;D;.

Sift4G

Benign

0.088

T;T;T;T;T

Polyphen

1.0, 1.0

.;D;D;D;.

Vest4

0.10

MPC

0.70

ClinPred

0.014

GERP RS

3.5

Varity_R

0.16

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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