Variant rs11188434 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015631.6(TCTN3):c.500-11A>T 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 0.153 in 1,597,844 control chromosomes in the GnomAD database, including 20,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2983 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17558 hom. )

Consequence

TCTN3
NM_015631.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.5724

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.552

Variant links:

Genes affected

TCTN3 (HGNC:24519): (tectonic family member 3) This gene encodes a member of the tectonic gene family which functions in Hedgehog signal transduction and development of the neural tube. Mutations in this gene have been associated with Orofaciodigital Syndrome IV and Joubert Syndrom 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]

TCTN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 10-95687730-T-A is Benign according to our data. Variant chr10-95687730-T-A is described in ClinVar as [Benign]. Clinvar id is 260669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-95687730-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN3	NM_015631.6 linkuse as main transcript	c.500-11A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN3	ENST00000371217.10 linkuse as main transcript	c.500-11A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015631.6	P2	Q6NUS6-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28219

AN:

152152

Hom.:

2984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.159

AC:

36990

AN:

231936

Hom.:

3366

AF XY:

0.162

AC XY:

20319

AN XY:

125504

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.149

AC:

215691

AN:

1445574

Hom.:

17558

Cov.:

AF XY:

0.151

AC XY:

108849

AN XY:

718524

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.0971

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.185

AC:

28233

AN:

152270

Hom.:

2983

Cov.:

AF XY:

0.183

AC XY:

13644

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.180

Hom.:

513

Bravo

AF:

0.191

Asia WGS

AF:

0.165

AC:

576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 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. -

Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.57

dbscSNV1_RF

Benign

0.62

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