Genetic Variant TEKT2:p.Ala229Gly (chr1-36086984-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014466.3(TEKT2):c.686C>G(p.Ala229Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A229V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TEKT2
NM_014466.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

Publications

10 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42192715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014466.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT2	NM_014466.3	MANE Select	c.686C>G	p.Ala229Gly	missense	Exon 6 of 10	NP_055281.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEKT2	ENST00000207457.8	TSL:1 MANE Select	c.686C>G	p.Ala229Gly	missense	Exon 6 of 10	ENSP00000207457.3	Q9UIF3
TEKT2	ENST00000902746.1		c.686C>G	p.Ala229Gly	missense	Exon 6 of 10	ENSP00000572805.1
TEKT2	ENST00000922202.1		c.686C>G	p.Ala229Gly	missense	Exon 6 of 10	ENSP00000592261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250898

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.28

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.69

M_CAP

Benign

0.0054

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

PhyloP100

2.9

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.24

Sift

Benign

0.085

Sift4G

Uncertain

0.052

Polyphen

0.57

Vest4

0.29

MutPred

0.79

Loss of stability (P = 0.0496)

MVP

0.095

MPC

0.12

ClinPred

0.26

GERP RS

3.6

PromoterAI

-0.0016

Neutral

(source)

Varity_R

0.43

gMVP

0.65

Mutation Taster

=60/40

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over