Variant 17-15312369-C-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.991G>T(p.Val331Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TEKT3
NM_031898.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

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=0.24383825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT3	NM_031898.3 linkuse as main transcript	c.991G>T	p.Val331Leu	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.991G>T	p.Val331Leu	missense_variant	7/9	1	NM_031898.3	P1
TEKT3	ENST00000338696.6 linkuse as main transcript	c.991G>T	p.Val331Leu	missense_variant	5/7	1		P1
TEKT3	ENST00000539245.5 linkuse as main transcript	c.493G>T	p.Val165Leu	missense_variant	8/8	5
TEKT3	ENST00000395931.6 linkuse as main transcript	c.*291G>T		3_prime_UTR_variant, NMD_transcript_variant	5/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000151

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

Jun 24, 2022

The c.991G>T (p.V331L) alteration is located in exon 7 (coding exon 5) of the TEKT3 gene. This alteration results from a G to T substitution at nucleotide position 991, causing the valine (V) at amino acid position 331 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

.;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

0.92

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.28

T;T;.

Polyphen

0.26

B;B;.

Vest4

0.26

MutPred

0.28

Loss of MoRF binding (P = 0.2921);Loss of MoRF binding (P = 0.2921);.;

MVP

0.31

MPC

0.25

ClinPred

0.74

GERP RS

5.8

Varity_R

0.55

gMVP

0.80

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