Genetic Variant TEKT2:p.Val6Ile (chr1-36084937-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014466.3(TEKT2):c.16G>A(p.Val6Ile) 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 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TEKT2
NM_014466.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0180

Publications

0 publications found

Variant links:

Genes affected

TEKT2 (HGNC:11725): (tektin 2) 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. This gene is expressed in the testis and its protein is localized to the flagella of the sperms, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

TEKT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036245257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3 link	c.16G>A	p.Val6Ile	missense_variant	Exon 2 of 10	ENST00000207457.8	NP_055281.2	Q9UIF3
TEKT2	XM_005270753.3 link	c.16G>A	p.Val6Ile	missense_variant	Exon 2 of 10		XP_005270810.1	Q9UIF3
TEKT2	XM_011541258.4 link	c.16G>A	p.Val6Ile	missense_variant	Exon 2 of 10		XP_011539560.1	Q9UIF3
TEKT2	XM_017001055.2 link	c.16G>A	p.Val6Ile	missense_variant	Exon 2 of 10		XP_016856544.1	Q9UIF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8 link	c.16G>A	p.Val6Ile	missense_variant	Exon 2 of 10	1	NM_014466.3	ENSP00000207457.3		Q9UIF3
TEKT2	ENST00000469024.1 link	n.16G>A		non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000434183.1		E9PRS9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251328

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

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.:

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

Mar 07, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.16G>A (p.V6I) alteration is located in exon 2 (coding exon 1) of the TEKT2 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the valine (V) at amino acid position 6 to be replaced by an isoleucine (I). 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

0.081

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.9

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.065

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.71

M_CAP

Benign

0.0035

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PhyloP100

-0.018

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.25

REVEL

Benign

0.072

Sift

Benign

0.39

Sift4G

Benign

0.39

Polyphen

0.063

Vest4

0.041

MutPred

0.24

Loss of MoRF binding (P = 0.1179);

MVP

0.055

MPC

0.073

ClinPred

0.017

GERP RS

0.67

Varity_R

0.022

gMVP

0.30

Mutation Taster

=97/3

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

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chr1-36084937-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over