17-6800943-C-T

Variant names:

• chr17-6800943-C-T
• rs1976763100
• NM_053285.2:c.853G>A

Variant summary

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

The NM_053285.2(TEKT1):​c.853G>A​(p.Val285Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEKT1 NM_053285.2 missense, splice_region
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

Genes affected

TEKT1 (HGNC:15534): (tektin 1) 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. This gene is predominantly expressed in the testis and in mouse, tektin 1 mRNA was localized to the spermatocytes and round spermatids in the seminiferous tubules, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT1	NM_053285.2	c.853G>A	p.Val285Ile	missense_variant, splice_region_variant	Exon 7 of 8	ENST00000338694.7	NP_444515.1
TEKT1	XM_011524027.4	c.853-709G>A		intron_variant	Intron 6 of 6		XP_011522329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT1	ENST00000338694.7	c.853G>A	p.Val285Ile	missense_variant, splice_region_variant	Exon 7 of 8	1	NM_053285.2	ENSP00000341346.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.853G>A (p.V285I) alteration is located in exon 7 (coding exon 6) of the TEKT1 gene. This alteration results from a G to A substitution at nucleotide position 853, causing the valine (V) at amino acid position 285 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Benign	0.46	T
Polyphen		0.38	B
Vest4		0.49
MutPred		0.56		Loss of methylation at K284 (P = 0.1003);
MVP		0.19
MPC		0.30
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1976763100; hg19: chr17-6704262;