17-6800863-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_053285.2(TEKT1):c.933G>T(p.Lys311Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,614,162 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (22 hom.)
• Consequence: TEKT1 NM_053285.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.367

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013628691).
• BP6: Variant 17-6800863-C-A is Benign according to our data. Variant chr17-6800863-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000671 (981/1461878) while in subpopulation EAS AF= 0.0221 (878/39694). AF 95% confidence interval is 0.0209. There are 22 homozygotes in gnomad4_exome. There are 507 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT1	NM_053285.2	c.933G>T	p.Lys311Asn	missense_variant	7/8	ENST00000338694.7
TEKT1	XM_011524027.4	c.853-629G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT1	ENST00000338694.7	c.933G>T	p.Lys311Asn	missense_variant	7/8	1	NM_053285.2	P1
TEKT1	ENST00000571744.1	c.187-11533G>T		intron_variant		3
TEKT1	ENST00000572291.1	c.239-629G>T		intron_variant		5
TEKT1	ENST00000575592.1	c.*524G>T		3_prime_UTR_variant, NMD_transcript_variant	6/7	2

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152166 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000700 AC: 176 AN: 251322 Hom.: 2 AF XY: 0.000655 AC XY: 89 AN XY: 135814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00837

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000671 AC: 981 AN: 1461878 Hom.: 22 Cov.: 31 AF XY: 0.000697 AC XY: 507 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0221

Gnomad4 SAS exome AF: 0.000649

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.000546

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152284 Hom.: 3 Cov.: 32 AF XY: 0.000537 AC XY: 40 AN XY: 74452

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000529 Hom.: 0

Bravo AF: 0.000438

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000972 AC: 118

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TEKT1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 31, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.0014
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.4	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.21
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.11	B
Vest4		0.82
MutPred		0.71		Loss of ubiquitination at K311 (P = 0.0134);
MVP		0.25
MPC		0.14
ClinPred		0.22	T
GERP RS		1.5
Varity_R		0.60
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs77092590; hg19: chr17-6704182;