16-10676081-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144674.2(TEKT5):c.964C>T(p.His322Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEKT5 NM_144674.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.192

Genes affected

TEKT5 (HGNC:26554): (tektin 5) Predicted to be involved in cilium assembly and cilium movement involved in cell motility. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1767129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT5	NM_144674.2	c.964C>T	p.His322Tyr	missense_variant	5/7	ENST00000283025.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT5	ENST00000283025.7	c.964C>T	p.His322Tyr	missense_variant	5/7	1	NM_144674.2	P1
TEKT5	ENST00000576638.1	c.283C>T	p.His95Tyr	missense_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 14, 2021

The c.964C>T (p.H322Y) alteration is located in exon 5 (coding exon 5) of the TEKT5 gene. This alteration results from a C to T substitution at nucleotide position 964, causing the histidine (H) at amino acid position 322 to be replaced by a tyrosine (Y). 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	0.069
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	11
Dann	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.045
Sift	Benign	0.038	D;.
Sift4G	Benign	0.47	T;.
Polyphen		0.10	B;.
Vest4		0.11
MutPred		0.41		Loss of disorder (P = 0.0447);.;
MVP		0.44
MPC		0.027
ClinPred		0.20	T
GERP RS		1.1
Varity_R		0.19
gMVP		0.38

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: chr16-10769938;