dbSNP rs3744395: TEKT1:p.Arg254Cys (chr17-6812923-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053285.2(TEKT1):c.760C>T(p.Arg254Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,926 control chromosomes in the GnomAD database, including 38,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3060 hom., cov: 33)

Exomes 𝑓: 0.21 ( 35150 hom. )

Consequence

TEKT1
NM_053285.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.974

Variant links:

Genes affected

TEKT1 (HGNC:15534): (tektin 1) 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 predominantly expressed in the testis and in mouse, tektin 1 mRNA was localized to the spermatocytes and round spermatids in the seminiferous tubules, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

TEKT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020502806).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT1	NM_053285.2 link	c.760C>T	p.Arg254Cys	missense_variant	Exon 6 of 8	ENST00000338694.7	NP_444515.1	Q969V4
TEKT1	XM_011524027.4 link	c.760C>T	p.Arg254Cys	missense_variant	Exon 6 of 7		XP_011522329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT1	ENST00000338694.7 link	c.760C>T	p.Arg254Cys	missense_variant	Exon 6 of 8	1	NM_053285.2	ENSP00000341346.2		Q969V4

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28912

AN:

152080

Hom.:

3063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.231

AC:

58050

AN:

251260

Hom.:

7492

AF XY:

0.228

AC XY:

30903

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.439

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.213

AC:

311558

AN:

1461728

Hom.:

35150

Cov.:

AF XY:

0.212

AC XY:

154156

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.190

AC:

28914

AN:

152198

Hom.:

3060

Cov.:

AF XY:

0.193

AC XY:

14323

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.202

Hom.:

8503

Bravo

AF:

0.191

TwinsUK

AF:

0.208

AC:

772

ALSPAC

AF:

0.193

AC:

744

ESP6500AA

AF:

0.123

AC:

541

ESP6500EA

AF:

0.207

AC:

1780

ExAC

AF:

0.228

AC:

27734

Asia WGS

AF:

0.317

AC:

1101

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

.;L

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.9

.;D

REVEL

Benign

0.080

Sift

Benign

0.13

.;T

Sift4G

Benign

0.12

T;T

Polyphen

0.037

.;B

Vest4

0.095

MPC

0.12

ClinPred

0.015

GERP RS

0.21

Varity_R

0.19

gMVP

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over