1-36084950-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014466.3(TEKT2):c.29G>A(p.Arg10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

TEKT2
NM_014466.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011222273).

BP6

Variant 1-36084950-G-A is Benign according to our data. Variant chr1-36084950-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3175741.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEKT2	NM_014466.3 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	2/10	ENST00000207457.8
TEKT2	XM_005270753.3 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	2/10
TEKT2	XM_011541258.4 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	2/10
TEKT2	XM_017001055.2 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT2	ENST00000207457.8 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	2/10	1	NM_014466.3	P1
TEKT2	ENST00000469024.1 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant, NMD_transcript_variant	2/10	2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

251316

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

318

AN:

1461724

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

199

AN XY:

727186

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:

0.00133

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000131

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.77

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.039

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.094

M_CAP

Benign

0.0068

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

1.5

REVEL

Benign

0.033

Sift

Benign

0.67

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.020

MVP

0.048

MPC

0.098

ClinPred

0.019

GERP RS

3.0

Varity_R

0.049

gMVP

0.19

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