17-15314213-T-G

Position:

• chr17-15314213-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_031898.3(TEKT3):​c.752A>C​(p.Gln251Pro) variant causes a missense change. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEKT3 NM_031898.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.96

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906
• PP5: Variant 17-15314213-T-G is Pathogenic according to our data. Variant chr17-15314213-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 2443975.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT3	NM_031898.3	c.752A>C	p.Gln251Pro	missense_variant	6/9	ENST00000395930.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT3	ENST00000395930.6	c.752A>C	p.Gln251Pro	missense_variant	6/9	1	NM_031898.3	P1
TEKT3	ENST00000338696.6	c.752A>C	p.Gln251Pro	missense_variant	4/7	1		P1
TEKT3	ENST00000539245.5	c.254A>C	p.Gln85Pro	missense_variant	7/8	5
TEKT3	ENST00000395931.6	c.*52A>C		3_prime_UTR_variant, NMD_transcript_variant	4/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 81 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	.;D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.4	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0090	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.84
MutPred		0.75		Gain of glycosylation at Q251 (P = 0.1041);Gain of glycosylation at Q251 (P = 0.1041);.;
MVP		0.56
MPC		0.70
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.98
gMVP		0.89

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: chr17-15217530;