Genetic Variant TEKT3:p.Gly282Val (chr17-15314120-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_031898.3(TEKT3):c.845G>T(p.Gly282Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,034 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

TEKT3
NM_031898.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86

Publications

32 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 81
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TEKT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.20346 (below the threshold of 3.09). Trascript score misZ: 0.91588 (below the threshold of 3.09). GenCC associations: The gene is linked to spermatogenic failure 81.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT3	NM_031898.3 link	c.845G>T	p.Gly282Val	missense_variant	Exon 6 of 9	ENST00000395930.6	NP_114104.1	Q9BXF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT3	ENST00000395930.6 link	c.845G>T	p.Gly282Val	missense_variant	Exon 6 of 9	1	NM_031898.3	ENSP00000379263.1		Q9BXF9

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

11970

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

T;T;T

Eigen

Benign

-0.013

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.67

.;T;T

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Benign

2.0

M;M;.

PhyloP100

5.9

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0090

D;D;D

Sift4G

Benign

0.29

T;T;.

Polyphen

0.15

B;B;.

Vest4

0.37

MutPred

0.43

Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);.;

MVP

0.19

MPC

0.43

ClinPred

0.90

GERP RS

5.4

Varity_R

0.53

gMVP

0.62

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over