rs796052142

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015631.6(TCTN3):c.152C>T(p.Ser51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000858 in 1,399,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S51S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

TCTN3
NM_015631.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

1 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
Joubert syndrome 18
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10284823).

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
TCTN3	NM_015631.6	MANE Select	c.152C>T	p.Ser51Leu	missense	Exon 1 of 14	NP_056446.4
TCTN3	NM_001410982.1		c.152C>T	p.Ser51Leu	missense	Exon 1 of 13	NP_001397911.1
TCTN3	NM_001143973.2		c.152C>T	p.Ser51Leu	missense	Exon 1 of 10	NP_001137445.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TCTN3	ENST00000371217.10	TSL:1 MANE Select	c.152C>T	p.Ser51Leu	missense	Exon 1 of 14	ENSP00000360261.5
TCTN3	ENST00000265993.13	TSL:1	c.206C>T	p.Ser69Leu	missense	Exon 1 of 14	ENSP00000265993.9
TCTN3	ENST00000614499.5	TSL:1	c.206C>T	p.Ser69Leu	missense	Exon 1 of 14	ENSP00000483364.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1399368

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

1078972

Other (OTH)

AF:

0.00

AC:

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.75

M_CAP

Benign

0.056

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

REVEL

Benign

0.22

Sift

Benign

0.15

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.076

MutPred

0.11

Loss of glycosylation at S51 (P = 0.0105)

MVP

0.86

MPC

0.098

ClinPred

0.12

GERP RS

3.6

PromoterAI

0.0057

Neutral

(source)

Varity_R

0.097

gMVP

0.41

Mutation Taster

=92/8

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over