rs2271233

Positions:

• chr17-6800802-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053285.2(TEKT1):​c.994G>A​(p.Val332Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 1,614,110 control chromosomes in the GnomAD database, including 4,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.056 (299 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4521 hom.)
• Consequence: TEKT1 NM_053285.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031917691).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT1	NM_053285.2	c.994G>A	p.Val332Ile	missense_variant	7/8	ENST00000338694.7	NP_444515.1
TEKT1	XM_011524027.4	c.853-568G>A		intron_variant			XP_011522329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEKT1	ENST00000338694.7	c.994G>A	p.Val332Ile	missense_variant	7/8	1	NM_053285.2	ENSP00000341346.2

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8550 AN: 152148 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0662

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0679

GnomAD3 exomes AF: 0.0644 AC: 16176 AN: 251124 Hom.: 684 AF XY: 0.0671 AC XY: 9106 AN XY: 135706

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0678

Gnomad EAS exome AF: 0.0478

Gnomad SAS exome AF: 0.0828

Gnomad FIN exome AF: 0.0463

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0696

GnomAD4 exome AF: 0.0760 AC: 111157 AN: 1461844 Hom.: 4521 Cov.: 32 AF XY: 0.0761 AC XY: 55377 AN XY: 727216

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0410

Gnomad4 ASJ exome AF: 0.0676

Gnomad4 EAS exome AF: 0.0330

Gnomad4 SAS exome AF: 0.0811

Gnomad4 FIN exome AF: 0.0460

Gnomad4 NFE exome AF: 0.0827

Gnomad4 OTH exome AF: 0.0689

GnomAD4 genome AF: 0.0562 AC: 8550 AN: 152266 Hom.: 299 Cov.: 32 AF XY: 0.0556 AC XY: 4137 AN XY: 74440

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0662

Gnomad4 EAS AF: 0.0447

Gnomad4 SAS AF: 0.0852

Gnomad4 FIN AF: 0.0434

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0763 Hom.: 1169

Bravo AF: 0.0536

TwinsUK AF: 0.0850 AC: 315

ALSPAC AF: 0.0934 AC: 360

ESP6500AA AF: 0.0154 AC: 68

ESP6500EA AF: 0.0807 AC: 694

ExAC AF: 0.0655 AC: 7954

Asia WGS AF: 0.0900 AC: 313 AN: 3478

EpiCase AF: 0.0855

EpiControl AF: 0.0834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.87
DEOGEN2	Benign	0.00048	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.65	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.053
Sift	Benign	0.42	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.070
ClinPred		0.00052	T
GERP RS		1.5
Varity_R		0.047
gMVP		0.054

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: rs2271233; hg19: chr17-6704121; COSMIC: COSV58623258; COSMIC: COSV58623258;