chr12-110628757-T-A

Position:

chr12-110628757-T-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001082538.3(TCTN1):c.473-10T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00658 in 1,586,524 control chromosomes in the GnomAD database, including 290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 130 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 160 hom. )

Consequence

TCTN1
NM_001082538.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.5244

Clinical Significance

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

Conservation

PhyloP100: 2.63

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 12-110628757-T-A is Benign according to our data. Variant chr12-110628757-T-A is described in ClinVar as [Benign]. Clinvar id is 160098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110628757-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN1	NM_001082538.3 linkuse as main transcript	c.473-10T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000397659.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN1	ENST00000397659.9 linkuse as main transcript	c.473-10T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001082538.3	A1	Q2MV58-2

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3734

AN:

152162

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00869

AC:

2117

AN:

243572

Hom.:

AF XY:

0.00766

AC XY:

1015

AN XY:

132520

show subpopulations

Gnomad AFR exome

AF:

0.0827

Gnomad AMR exome

AF:

0.00578

Gnomad ASJ exome

AF:

0.00372

Gnomad EAS exome

AF:

0.000281

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.000206

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00466

AC:

6690

AN:

1434244

Hom.:

160

Cov.:

AF XY:

0.00473

AC XY:

3384

AN XY:

715104

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.00647

Gnomad4 ASJ exome

AF:

0.00320

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.000298

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.00860

GnomAD4 genome

AF:

0.0246

AC:

3745

AN:

152280

Hom.:

130

Cov.:

AF XY:

0.0237

AC XY:

1763

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0798

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.0284

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 02, 2016	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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Joubert syndrome 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.3

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.52

dbscSNV1_RF

Benign

0.61

SpliceAI score (max)

0.13

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