Genetic Variant TEKT2:p.Gln52Lys (chr1-36085075-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014466.3(TEKT2):c.154C>A(p.Gln52Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000205 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. Q52E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TEKT2
NM_014466.3 missense, splice_region

Scores

Splicing: ADA: 0.1536

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.117453754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3 link	c.154C>A	p.Gln52Lys	missense_variant, splice_region_variant	Exon 2 of 10	ENST00000207457.8	NP_055281.2	Q9UIF3
TEKT2	XM_005270753.3 link	c.154C>A	p.Gln52Lys	missense_variant, splice_region_variant	Exon 2 of 10		XP_005270810.1	Q9UIF3
TEKT2	XM_011541258.4 link	c.154C>A	p.Gln52Lys	missense_variant, splice_region_variant	Exon 2 of 10		XP_011539560.1	Q9UIF3
TEKT2	XM_017001055.2 link	c.154C>A	p.Gln52Lys	missense_variant, splice_region_variant	Exon 2 of 10		XP_016856544.1	Q9UIF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8 link	c.154C>A	p.Gln52Lys	missense_variant, splice_region_variant	Exon 2 of 10	1	NM_014466.3	ENSP00000207457.3		Q9UIF3
TEKT2	ENST00000469024.1 link	n.154C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000434183.1		E9PRS9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.048

Eigen

Benign

-0.16

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.65

REVEL

Benign

0.14

Sift

Benign

0.57

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.22

MutPred

0.47

Gain of ubiquitination at Q52 (P = 0.009);

MVP

0.12

MPC

0.11

ClinPred

0.88

GERP RS

5.5

Varity_R

0.65

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.15

dbscSNV1_RF

Benign

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over