Genetic Variant TEKT2:p.Gln374His (chr1-36088015-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014466.3(TEKT2):c.1122G>T(p.Gln374His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TEKT2
NM_014466.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.488

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3 link	c.1122G>T	p.Gln374His	missense_variant	Exon 10 of 10	ENST00000207457.8	NP_055281.2	Q9UIF3
TEKT2	XM_005270753.3 link	c.1122G>T	p.Gln374His	missense_variant	Exon 10 of 10		XP_005270810.1	Q9UIF3
TEKT2	XM_011541258.4 link	c.1122G>T	p.Gln374His	missense_variant	Exon 10 of 10		XP_011539560.1	Q9UIF3
TEKT2	XM_017001055.2 link	c.1122G>T	p.Gln374His	missense_variant	Exon 10 of 10		XP_016856544.1	Q9UIF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEKT2	ENST00000207457.8 link	c.1122G>T	p.Gln374His	missense_variant	Exon 10 of 10	1	NM_014466.3	ENSP00000207457.3	Q9UIF3
TEKT2	ENST00000469024.1 link	n.*926G>T		non_coding_transcript_exon_variant	Exon 10 of 10	2		ENSP00000434183.1	E9PRS9
TEKT2	ENST00000473120.1 link	c.*204G>T		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000432793.1	H0YD25
TEKT2	ENST00000469024.1 link	n.*926G>T		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000434183.1	E9PRS9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460026

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111678

Other (OTH)

AF:

0.00

AC:

AN:

60348

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 12, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1122G>T (p.Q374H) alteration is located in exon 10 (coding exon 9) of the TEKT2 gene. This alteration results from a G to T substitution at nucleotide position 1122, causing the glutamine (Q) at amino acid position 374 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.021

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.72

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.49

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.4

REVEL

Benign

0.15

Sift

Benign

0.086

Sift4G

Benign

0.072

Polyphen

0.94

Vest4

0.53

MutPred

0.63

Gain of methylation at R372 (P = 0.0588);

MVP

0.24

MPC

0.35

ClinPred

0.71

GERP RS

2.0

Varity_R

0.19

gMVP

0.24

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr1-36088015-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over