Variant rs61737888 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000371217.10(TCTN3):c.21G>A(p.Ala7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,551,700 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A7A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0030 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 3 hom. )

Consequence

TCTN3
ENST00000371217.10 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.247

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 10-95693879-C-T is Benign according to our data. Variant chr10-95693879-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.247 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00303 (461/152332) while in subpopulation AFR AF= 0.00902 (375/41566). AF 95% confidence interval is 0.00827. There are 4 homozygotes in gnomad4. There are 221 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN3	NM_015631.6 linkuse as main transcript	c.21G>A	p.Ala7=	synonymous_variant	1/14	ENST00000371217.10	NP_056446.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN3	ENST00000371217.10 linkuse as main transcript	c.21G>A	p.Ala7=	synonymous_variant	1/14	1	NM_015631.6	ENSP00000360261	P2	Q6NUS6-1

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00905

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00464

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:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000772

AC:

120

AN:

155482

Hom.:

AF XY:

0.000691

AC XY:

AN XY:

82536

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.00154

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:

0.0000166

Gnomad OTH exome

AF:

0.000457

GnomAD4 exome

AF:

0.000282

AC:

394

AN:

1399368

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

171

AN XY:

690192

show subpopulations

Gnomad4 AFR exome

AF:

0.00807

Gnomad4 AMR exome

AF:

0.00216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.000862

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152332

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00902

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00414

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2017	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. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

not provided

Benign:1

Likely 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

-0.29

CADD

Benign

6.2

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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