17-15304047-T-G

Variant names:

• chr17-15304047-T-G
• rs13961
• NM_031898.3:c.1362A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031898.3(TEKT3):​c.1362A>C​(p.Thr454Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,613,930 control chromosomes in the GnomAD database, including 483,891 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47181 hom., cov: 31)
  • Exomes 𝑓: 0.77 (436710 hom.)
• Consequence: TEKT3 NM_031898.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 16 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)

ENSG00000265445 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.291 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT3	NM_031898.3	c.1362A>C	p.Thr454Thr	synonymous_variant	Exon 9 of 9	ENST00000395930.6	NP_114104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT3	ENST00000395930.6	c.1362A>C	p.Thr454Thr	synonymous_variant	Exon 9 of 9	1	NM_031898.3	ENSP00000379263.1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119578 AN: 151938 Hom.: 47158 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.772

GnomAD2 exomes AF: 0.773 AC: 194334 AN: 251436 AF XY: 0.773

Gnomad AFR exome AF: 0.837

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.691

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.759

GnomAD4 exome AF: 0.773 AC: 1129322 AN: 1461874 Hom.: 436710 Cov.: 69 AF XY: 0.773 AC XY: 562065 AN XY: 727238

African (AFR) AF: 0.834 AC: 27917 AN: 33480

American (AMR) AF: 0.775 AC: 34676 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19578 AN: 26136

East Asian (EAS) AF: 0.685 AC: 27194 AN: 39698

South Asian (SAS) AF: 0.805 AC: 69399 AN: 86256

European-Finnish (FIN) AF: 0.796 AC: 42535 AN: 53420

Middle Eastern (MID) AF: 0.748 AC: 4312 AN: 5766

European-Non Finnish (NFE) AF: 0.771 AC: 857292 AN: 1111998

Other (OTH) AF: 0.769 AC: 46419 AN: 60396

GnomAD4 genome AF: 0.787 AC: 119643 AN: 152056 Hom.: 47181 Cov.: 31 AF XY: 0.786 AC XY: 58412 AN XY: 74320

African (AFR) AF: 0.834 AC: 34601 AN: 41474

American (AMR) AF: 0.777 AC: 11879 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2575 AN: 3472

East Asian (EAS) AF: 0.699 AC: 3590 AN: 5134

South Asian (SAS) AF: 0.799 AC: 3844 AN: 4812

European-Finnish (FIN) AF: 0.811 AC: 8571 AN: 10570

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51971 AN: 67990

Other (OTH) AF: 0.772 AC: 1625 AN: 2106

Alfa AF: 0.767 Hom.: 52579

Bravo AF: 0.784

Asia WGS AF: 0.763 AC: 2655 AN: 3478

EpiCase AF: 0.756

EpiControl AF: 0.762

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.85
DANN	Benign	0.31
PhyloP100		-0.29
Mutation Taster		=100/0	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: rs13961; hg19: chr17-15207364; COSMIC: COSV58625938;