17-15304042-T-C

Position:

• chr17-15304042-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031898.3(TEKT3):​c.1367A>G​(p.Glu456Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEKT3 NM_031898.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

Genes affected

TEKT3 (HGNC:14293): (tektin 3) 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. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT3	NM_031898.3	c.1367A>G	p.Glu456Gly	missense_variant	9/9	ENST00000395930.6
LOC124903932	XR_007065633.1	n.298-817T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT3	ENST00000395930.6	c.1367A>G	p.Glu456Gly	missense_variant	9/9	1	NM_031898.3	P1
	ENST00000654786.1	n.138-3619T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.1367A>G (p.E456G) alteration is located in exon 9 (coding exon 7) of the TEKT3 gene. This alteration results from a A to G substitution at nucleotide position 1367, causing the glutamic acid (E) at amino acid position 456 to be replaced by a glycine (G). 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	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.23	T;T
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.8	H;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.94
MutPred		0.56		Loss of ubiquitination at K452 (P = 0.0618);Loss of ubiquitination at K452 (P = 0.0618);
MVP		0.64
MPC		0.69
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.86
gMVP		0.67

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.

Other links and lift over

hg19: chr17-15207359;