Variant 2-94871854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144705.4(TEKT4):c.275G>A(p.Gly92Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,450,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TEKT4
NM_144705.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42322886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT4	NM_144705.4 linkuse as main transcript	c.275G>A	p.Gly92Asp	missense_variant	1/6	ENST00000295201.5	NP_653306.1
LOC442028	NR_037597.1 linkuse as main transcript	n.1318-1157C>T		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.275G>A	p.Gly92Asp	missense_variant	1/6	1	NM_144705.4	ENSP00000295201	P1
	ENST00000568768.5 linkuse as main transcript	n.2256C>T		non_coding_transcript_exon_variant	8/8	1
TEKT4	ENST00000468063.1 linkuse as main transcript	n.422G>A		non_coding_transcript_exon_variant	1/6	2
	ENST00000582835.1 linkuse as main transcript	n.1317-1157C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1450852

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

721726

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:

0.0000144

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

Aug 17, 2022

The c.275G>A (p.G92D) alteration is located in exon 1 (coding exon 1) of the TEKT4 gene. This alteration results from a G to A substitution at nucleotide position 275, causing the glycine (G) at amino acid position 92 to be replaced by an aspartic acid (D). 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

0.27

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

0.044

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.84

M_CAP

Benign

0.0040

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.21

Sift

Uncertain

0.012

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.30

MutPred

0.41

Loss of MoRF binding (P = 0.0397);

MVP

0.32

MPC

0.25

ClinPred

0.93

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.43

gMVP

0.62

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

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