dbSNP rs10786229: TCTN3:p.Thr201Thr (chr10-95687616-A-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015631.6(TCTN3):c.603T>A(p.Thr201Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,613,760 control chromosomes in the GnomAD database, including 93,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10154 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83540 hom. )

Consequence

TCTN3
NM_015631.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0850

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
orofaciodigital syndrome IV
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
Joubert syndrome 18
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TCTN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-95687616-A-T is Benign according to our data. Variant chr10-95687616-A-T is described in ClinVar as Benign. ClinVar VariationId is 130577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.085 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCTN3	NM_015631.6	MANE Select	c.603T>A	p.Thr201Thr	synonymous	Exon 4 of 14	NP_056446.4	Q6NUS6-1
TCTN3	NM_001410982.1		c.603T>A	p.Thr201Thr	synonymous	Exon 4 of 13	NP_001397911.1	A0A7P0TB57
TCTN3	NM_001143973.2		c.500-457T>A		intron	N/A	NP_001137445.1	Q6NUS6-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCTN3	ENST00000371217.10	TSL:1 MANE Select	c.603T>A	p.Thr201Thr	synonymous	Exon 4 of 14	ENSP00000360261.5	Q6NUS6-1
TCTN3	ENST00000265993.13	TSL:1	c.657T>A	p.Thr219Thr	synonymous	Exon 4 of 14	ENSP00000265993.9	A0A0C4DFN5
TCTN3	ENST00000614499.5	TSL:1	c.657T>A	p.Thr219Thr	synonymous	Exon 4 of 14	ENSP00000483364.2	A0A804G9W2

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53821

AN:

151956

Hom.:

10140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.403

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.349

AC:

87726

AN:

251200

AF XY:

0.352

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.717

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.331

AC:

483506

AN:

1461686

Hom.:

83540

Cov.:

AF XY:

0.332

AC XY:

241588

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.408

AC:

13665

AN:

33472

American (AMR)

AF:

0.227

AC:

10129

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

10664

AN:

26134

East Asian (EAS)

AF:

0.656

AC:

26036

AN:

39692

South Asian (SAS)

AF:

0.361

AC:

31162

AN:

86222

European-Finnish (FIN)

AF:

0.290

AC:

15493

AN:

53412

Middle Eastern (MID)

AF:

0.395

AC:

2279

AN:

5768

European-Non Finnish (NFE)

AF:

0.317

AC:

352673

AN:

1111924

Other (OTH)

AF:

0.354

AC:

21405

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

16921

33842

50763

67684

84605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11636

23272

34908

46544

58180

<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:

0.354

AC:

53883

AN:

152074

Hom.:

10154

Cov.:

AF XY:

0.352

AC XY:

26186

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.408

AC:

16929

AN:

41482

American (AMR)

AF:

0.273

AC:

4171

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

1398

AN:

3468

East Asian (EAS)

AF:

0.697

AC:

3602

AN:

5166

South Asian (SAS)

AF:

0.363

AC:

1748

AN:

4820

European-Finnish (FIN)

AF:

0.285

AC:

3007

AN:

10566

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21887

AN:

67980

Other (OTH)

AF:

0.369

AC:

776

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1740

3480

5219

6959

8699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.334

Hom.:

2810

Bravo

AF:

0.357

Asia WGS

AF:

0.520

AC:

1805

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.328

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (1)

Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.8

(source)

DANN

Benign

0.32

PhyloP100

-0.085

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over