dbSNP rs2271233: TEKT1:p.Val332Ile (chr17-6800802-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053285.2(TEKT1):c.994G>A(p.Val332Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 1,614,110 control chromosomes in the GnomAD database, including 4,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.056 ( 299 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4521 hom. )

Consequence

TEKT1
NM_053285.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.402

Publications

28 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031917691).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT1	NM_053285.2 link	c.994G>A	p.Val332Ile	missense_variant	Exon 7 of 8	ENST00000338694.7	NP_444515.1
TEKT1	XM_011524027.4 link	c.853-568G>A		intron_variant	Intron 6 of 6		XP_011522329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT1	ENST00000338694.7 link	c.994G>A	p.Val332Ile	missense_variant	Exon 7 of 8	1	NM_053285.2	ENSP00000341346.2

Frequencies

GnomAD3 genomes

AF:

0.0562

AC:

8550

AN:

152148

Hom.:

300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0662

Gnomad EAS

AF:

0.0446

Gnomad SAS

AF:

0.0845

Gnomad FIN

AF:

0.0434

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.0679

GnomAD2 exomes

AF:

0.0644

AC:

16176

AN:

251124

AF XY:

0.0671

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.0383

Gnomad ASJ exome

AF:

0.0678

Gnomad EAS exome

AF:

0.0478

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.0803

Gnomad OTH exome

AF:

0.0696

GnomAD4 exome

AF:

0.0760

AC:

111157

AN:

1461844

Hom.:

4521

Cov.:

AF XY:

0.0761

AC XY:

55377

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0120

AC:

403

AN:

33480

American (AMR)

AF:

0.0410

AC:

1835

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0676

AC:

1767

AN:

26134

East Asian (EAS)

AF:

0.0330

AC:

1309

AN:

39700

South Asian (SAS)

AF:

0.0811

AC:

6997

AN:

86254

European-Finnish (FIN)

AF:

0.0460

AC:

2458

AN:

53420

Middle Eastern (MID)

AF:

0.0513

AC:

296

AN:

5766

European-Non Finnish (NFE)

AF:

0.0827

AC:

91933

AN:

1111972

Other (OTH)

AF:

0.0689

AC:

4159

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

5968

11936

17904

23872

29840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3340

6680

10020

13360

16700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0562

AC:

8550

AN:

152266

Hom.:

299

Cov.:

AF XY:

0.0556

AC XY:

4137

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0157

AC:

653

AN:

41558

American (AMR)

AF:

0.0528

AC:

807

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0662

AC:

230

AN:

3472

East Asian (EAS)

AF:

0.0447

AC:

232

AN:

5188

South Asian (SAS)

AF:

0.0852

AC:

410

AN:

4810

European-Finnish (FIN)

AF:

0.0434

AC:

461

AN:

10610

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0811

AC:

5513

AN:

68016

Other (OTH)

AF:

0.0681

AC:

144

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

425

851

1276

1702

2127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0726

Hom.:

1495

Bravo

AF:

0.0536

TwinsUK

AF:

0.0850

AC:

315

ALSPAC

AF:

0.0934

AC:

360

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.0807

AC:

694

ExAC

AF:

0.0655

AC:

7954

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

EpiCase

AF:

0.0855

EpiControl

AF:

0.0834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.9

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.00048

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.65

PhyloP100

-0.40

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.88

REVEL

Benign

0.053

Sift

Benign

0.42

Sift4G

Benign

0.25

Vest4

0.035

ClinPred

0.00052

GERP RS

1.5

Varity_R

0.047

gMVP

0.054

Mutation Taster

=99/1

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over