12-110628757-TAAA-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001082538.3(TCTN1):c.473-6_473-4delAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,586,552 control chromosomes in the GnomAD database, including 339 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 317 hom. )

Consequence

TCTN1
NM_001082538.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.67

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 12-110628757-TAAA-T is Benign according to our data. Variant chr12-110628757-TAAA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.0172

AC:

4196

AN:

243572

AF XY:

0.0128

show subpopulations

Gnomad AFR exome

AF:

0.00151

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000618

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000722

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00355

AC:

5085

AN:

1434266

Hom.:

317

AF XY:

0.00293

AC XY:

2097

AN XY:

715120

show subpopulations

African (AFR)

AF:

0.000790

AC:

AN:

32906

American (AMR)

AF:

0.108

AC:

4801

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25958

East Asian (EAS)

AF:

0.00223

AC:

AN:

39452

South Asian (SAS)

AF:

0.000117

AC:

AN:

85478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

0.0000358

AC:

AN:

1090594

Other (OTH)

AF:

0.00203

AC:

121

AN:

59530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

196

393

589

786

982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00553

AC:

842

AN:

152286

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

474

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41554

American (AMR)

AF:

0.0490

AC:

750

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68014

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000875

Hom.:

Bravo

AF:

0.0108

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 10, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jan 13, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 06, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel-Gruber syndrome;C0431399:Joubert syndrome

Benign:1

Feb 02, 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

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over