17-6800802-C-T

Variant names:

• chr17-6800802-C-T
• rs2271233
• NM_053285.2:c.994G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053285.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT1	NM_053285.2	MANE Select	c.994G>A	p.Val332Ile	missense	Exon 7 of 8	NP_444515.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT1	ENST00000338694.7	TSL:1 MANE Select	c.994G>A	p.Val332Ile	missense	Exon 7 of 8	ENSP00000341346.2
	TEKT1	ENST00000575592.1	TSL:2	n.*585G>A		non_coding_transcript_exon	Exon 6 of 7	ENSP00000460359.1
	TEKT1	ENST00000575592.1	TSL:2	n.*585G>A		3_prime_UTR	Exon 6 of 7	ENSP00000460359.1

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

GnomAD2 exomes AF: 0.0644 AC: 16176 AN: 251124 AF XY: 0.0671

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 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

African (AFR) AF: 0.0120 AC: 403 AN: 33480

American (AMR) AF: 0.0410 AC: 1835 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1767 AN: 26134

East Asian (EAS) AF: 0.0330 AC: 1309 AN: 39700

South Asian (SAS) AF: 0.0811 AC: 6997 AN: 86254

European-Finnish (FIN) AF: 0.0460 AC: 2458 AN: 53420

Middle Eastern (MID) AF: 0.0513 AC: 296 AN: 5766

European-Non Finnish (NFE) AF: 0.0827 AC: 91933 AN: 1111972

Other (OTH) AF: 0.0689 AC: 4159 AN: 60394

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

African (AFR) AF: 0.0157 AC: 653 AN: 41558

American (AMR) AF: 0.0528 AC: 807 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 230 AN: 3472

East Asian (EAS) AF: 0.0447 AC: 232 AN: 5188

South Asian (SAS) AF: 0.0852 AC: 410 AN: 4810

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10610

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5513 AN: 68016

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0726 Hom.: 1495

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 v4.9

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
PhyloP100		-0.40
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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