Variant 17-15312296-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031898.3(TEKT3):c.1064C>T(p.Ala355Val) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TEKT3
NM_031898.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Variant links:

Genes affected

TEKT3 (HGNC:14293): (tektin 3) This gene product belongs to the tektin family of proteins. Tektins comprise a family of filament-forming proteins that are coassembled with tubulins to form ciliary and flagellar microtubules. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

TEKT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14480308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT3	NM_031898.3 linkuse as main transcript	c.1064C>T	p.Ala355Val	missense_variant	7/9	ENST00000395930.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TEKT3	ENST00000395930.6 linkuse as main transcript	c.1064C>T	p.Ala355Val	missense_variant	7/9	1	NM_031898.3	P1
TEKT3	ENST00000338696.6 linkuse as main transcript	c.1064C>T	p.Ala355Val	missense_variant	5/7	1		P1
TEKT3	ENST00000539245.5 linkuse as main transcript	c.566C>T	p.Ala189Val	missense_variant	8/8	5
TEKT3	ENST00000395931.6 linkuse as main transcript	c.*364C>T		3_prime_UTR_variant, NMD_transcript_variant	5/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251338

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

Cov.:

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.1064C>T (p.A355V) alteration is located in exon 7 (coding exon 5) of the TEKT3 gene. This alteration results from a C to T substitution at nucleotide position 1064, causing the alanine (A) at amino acid position 355 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.068

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.3

L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.46

N;N;N

REVEL

Benign

0.074

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.65

T;T;.

Polyphen

0.014

B;B;.

Vest4

0.17

MutPred

0.40

Loss of ubiquitination at K358 (P = 0.051);Loss of ubiquitination at K358 (P = 0.051);.;

MVP

0.25

MPC

0.18

ClinPred

0.11

GERP RS

2.3

Varity_R

0.085

gMVP

0.61

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