17-15312435-G-C

Position:

• chr17-15312435-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031898.3(TEKT3):​c.925C>G​(p.Leu309Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEKT3 NM_031898.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

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]

ACMG classification

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=0.3543005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT3	NM_031898.3	c.925C>G	p.Leu309Val	missense_variant	7/9	ENST00000395930.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT3	ENST00000395930.6	c.925C>G	p.Leu309Val	missense_variant	7/9	1	NM_031898.3	P1
TEKT3	ENST00000338696.6	c.925C>G	p.Leu309Val	missense_variant	5/7	1		P1
TEKT3	ENST00000539245.5	c.427C>G	p.Leu143Val	missense_variant	8/8	5
TEKT3	ENST00000395931.6	c.*225C>G		3_prime_UTR_variant, NMD_transcript_variant	5/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Nov 19, 2022

The c.925C>G (p.L309V) alteration is located in exon 7 (coding exon 5) of the TEKT3 gene. This alteration results from a C to G substitution at nucleotide position 925, causing the leucine (L) at amino acid position 309 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.74	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.081	T;T;T
Sift4G	Benign	0.50	T;T;.
Polyphen		0.15	B;B;.
Vest4		0.46
MVP		0.26
MPC		0.45
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.49
gMVP		0.71

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: chr17-15215752; COSMIC: COSV58628228; COSMIC: COSV58628228;