17-15331578-C-T

Variant names:

• chr17-15331578-C-T
• rs7226363
• NM_031898.3:c.8G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

The NM_031898.3(TEKT3):​c.8G>A​(p.Arg3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,608,672 control chromosomes in the GnomAD database, including 41,090 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 0.21 (3366 hom., cov: 31)
  • Exomes 𝑓: 0.23 (37724 hom.)
• Consequence: TEKT3 NM_031898.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 17 publications found

Genes affected

TEKT3 (HGNC:14293): (tektin 3) 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. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

TEKT3 Gene-Disease associations (from GenCC):

• spermatogenic failure 81

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.20346 (below the threshold of 3.09). Trascript score misZ: 0.91588 (below the threshold of 3.09). GenCC associations: The gene is linked to spermatogenic failure 81.
• BP4: Computational evidence support a benign effect (MetaRNN=0.015797138).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT3	NM_031898.3	c.8G>A	p.Arg3His	missense_variant	Exon 3 of 9	ENST00000395930.6	NP_114104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT3	ENST00000395930.6	c.8G>A	p.Arg3His	missense_variant	Exon 3 of 9	1	NM_031898.3	ENSP00000379263.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31410 AN: 151828 Hom.: 3363 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.215 AC: 52724 AN: 244676 AF XY: 0.219

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.259

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.226 AC: 328996 AN: 1456726 Hom.: 37724 Cov.: 33 AF XY: 0.227 AC XY: 164217 AN XY: 724142

African (AFR) AF: 0.158 AC: 5268 AN: 33306

American (AMR) AF: 0.142 AC: 6265 AN: 44174

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6406 AN: 25952

East Asian (EAS) AF: 0.262 AC: 10390 AN: 39624

South Asian (SAS) AF: 0.219 AC: 18832 AN: 85918

European-Finnish (FIN) AF: 0.204 AC: 10844 AN: 53124

Middle Eastern (MID) AF: 0.249 AC: 1426 AN: 5734

European-Non Finnish (NFE) AF: 0.231 AC: 255851 AN: 1108732

Other (OTH) AF: 0.228 AC: 13714 AN: 60162

GnomAD4 genome AF: 0.207 AC: 31421 AN: 151946 Hom.: 3366 Cov.: 31 AF XY: 0.206 AC XY: 15307 AN XY: 74274

African (AFR) AF: 0.164 AC: 6779 AN: 41436

American (AMR) AF: 0.169 AC: 2574 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1299 AN: 5152

South Asian (SAS) AF: 0.224 AC: 1075 AN: 4800

European-Finnish (FIN) AF: 0.189 AC: 1999 AN: 10564

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16124 AN: 67938

Other (OTH) AF: 0.219 AC: 463 AN: 2114

Alfa AF: 0.234 Hom.: 9400

Bravo AF: 0.204

TwinsUK AF: 0.241 AC: 893

ALSPAC AF: 0.232 AC: 894

ESP6500AA AF: 0.158 AC: 696

ESP6500EA AF: 0.242 AC: 2077

ExAC AF: 0.217 AC: 26315

Asia WGS AF: 0.225 AC: 780 AN: 3478

EpiCase AF: 0.246

EpiControl AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.20
DANN	Benign	0.80
DEOGEN2	Benign	0.014	T;T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.31	.;T;T;T;T
MetaRNN	Benign	0.016	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;.;.;.
PhyloP100		0.80
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.34	N;N;N;N;N
REVEL	Benign	0.090
Sift	Benign	0.13	T;T;T;T;T
Sift4G	Benign	0.064	T;T;.;D;T
Polyphen		0.21	B;B;.;.;.
Vest4		0.022
MPC		0.18
ClinPred		0.025	T
GERP RS		-11
PromoterAI		-0.0057	Neutral
Varity_R		0.031
gMVP		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7226363; hg19: chr17-15234895; COSMIC: COSV58626142;