1-36085057-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014466.3(TEKT2):c.136C>T(p.Arg46Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0135 in 1,614,098 control chromosomes in the GnomAD database, including 1,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.031 ( 243 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1130 hom. )

Consequence

TEKT2
NM_014466.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.75

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019831061).

BP6

Variant 1-36085057-C-T is Benign according to our data. Variant chr1-36085057-C-T is described in ClinVar as [Benign]. Clinvar id is 1244486.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEKT2	NM_014466.3 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	2/10	ENST00000207457.8
TEKT2	XM_005270753.3 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	2/10
TEKT2	XM_011541258.4 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	2/10
TEKT2	XM_017001055.2 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT2	ENST00000207457.8 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	2/10	1	NM_014466.3	P1
TEKT2	ENST00000469024.1 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant, NMD_transcript_variant	2/10	2

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4710

AN:

152198

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0329

AC:

8260

AN:

251256

Hom.:

617

AF XY:

0.0285

AC XY:

3878

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.0456

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.00617

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0117

AC:

17116

AN:

1461780

Hom.:

1130

Cov.:

AF XY:

0.0111

AC XY:

8108

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0578

Gnomad4 AMR exome

AF:

0.0458

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.00776

Gnomad4 FIN exome

AF:

0.0273

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.0237

GnomAD4 genome

AF:

0.0310

AC:

4721

AN:

152318

Hom.:

243

Cov.:

AF XY:

0.0327

AC XY:

2438

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0589

Gnomad4 AMR

AF:

0.0344

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.00201

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0130

Hom.:

279

Bravo

AF:

0.0344

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0586

AC:

258

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.0310

AC:

3761

Asia WGS

AF:

0.102

AC:

355

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2021

This variant is associated with the following publications: (PMID: 26584823) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

4.5e-10

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.16

Sift

Uncertain

0.013

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.13

MPC

0.22

ClinPred

0.023

GERP RS

3.7

Varity_R

0.59

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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