Variant chr1-36085859-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000207457.8(TEKT2):c.306C>G(p.Asn102Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,844 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

TEKT2
ENST00000207457.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040720254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT2	NM_014466.3 linkuse as main transcript	c.306C>G	p.Asn102Lys	missense_variant	4/10	ENST00000207457.8	NP_055281.2	Q9UIF3
TEKT2	XM_005270753.3 linkuse as main transcript	c.306C>G	p.Asn102Lys	missense_variant	4/10		XP_005270810.1	Q9UIF3
TEKT2	XM_011541258.4 linkuse as main transcript	c.306C>G	p.Asn102Lys	missense_variant	4/10		XP_011539560.1	Q9UIF3
TEKT2	XM_017001055.2 linkuse as main transcript	c.306C>G	p.Asn102Lys	missense_variant	4/10		XP_016856544.1	Q9UIF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEKT2	ENST00000207457.8 linkuse as main transcript	c.306C>G	p.Asn102Lys	missense_variant	4/10	1	NM_014466.3	ENSP00000207457.3	Q9UIF3
TEKT2	ENST00000469024.1 linkuse as main transcript	n.*110C>G		non_coding_transcript_exon_variant	4/10	2		ENSP00000434183.1	E9PRS9
TEKT2	ENST00000469024.1 linkuse as main transcript	n.*110C>G		3_prime_UTR_variant	4/10	2		ENSP00000434183.1	E9PRS9

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000160

AC:

AN:

249802

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000762

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.0000862

AC:

126

AN:

1461586

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.000940

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000105

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.00837

AC:

AN:

3478

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

May 31, 2023

The c.306C>G (p.N102K) alteration is located in exon 4 (coding exon 3) of the TEKT2 gene. This alteration results from a C to G substitution at nucleotide position 306, causing the asparagine (N) at amino acid position 102 to be replaced by a lysine (K). 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

0.26

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.050

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

M_CAP

Benign

0.0086

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.22

REVEL

Benign

0.077

Sift

Benign

0.12

Sift4G

Benign

0.44

Polyphen

0.067

Vest4

0.44

MutPred

0.66

Gain of ubiquitination at N102 (P = 0.017);

MVP

0.18

MPC

0.11

ClinPred

0.033

GERP RS

3.9

Varity_R

0.19

gMVP

0.55

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