Variant 2-94872075-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144705.4(TEKT4):c.496A>G(p.Lys166Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TEKT4
NM_144705.4 missense, splice_region

Scores

Splicing: ADA: 0.08788

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

TEKT4 (HGNC:31012): (tektin 4) Predicted to be involved in cilium assembly and cilium movement involved in cell motility. Predicted to act upstream of or within regulation of brood size. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TEKT4 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT4	NM_144705.4 linkuse as main transcript	c.496A>G	p.Lys166Glu	missense_variant, splice_region_variant	1/6	ENST00000295201.5	NP_653306.1
LOC442028	NR_037597.1 linkuse as main transcript	n.1317+1314T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TEKT4	ENST00000295201.5 linkuse as main transcript	c.496A>G	p.Lys166Glu	missense_variant, splice_region_variant	1/6	1	NM_144705.4	ENSP00000295201	P1
	ENST00000568768.5 linkuse as main transcript	n.2035T>C		non_coding_transcript_exon_variant	8/8	1
TEKT4	ENST00000468063.1 linkuse as main transcript	n.643A>G		splice_region_variant, non_coding_transcript_exon_variant	1/6	2
	ENST00000582835.1 linkuse as main transcript	n.1316+1314T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1388372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683964

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:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.496A>G (p.K166E) alteration is located in exon 1 (coding exon 1) of the TEKT4 gene. This alteration results from a A to G substitution at nucleotide position 496, causing the lysine (K) at amino acid position 166 to be replaced by a glutamic acid (E). 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

0.21

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.21

Eigen_PC

Benign

-0.0033

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

M_CAP

Benign

0.0078

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.24

Sift

Benign

0.035

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.22

MutPred

0.81

Loss of ubiquitination at K166 (P = 0.0233);

MVP

0.28

MPC

0.25

ClinPred

0.99

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Varity_R

0.50

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.088

dbscSNV1_RF

Benign

0.23

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: 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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over