17-15314120-C-G

Variant names:

• chr17-15314120-C-G
• rs230898
• NM_031898.3:c.845G>C

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.845G>C​(p.Gly282Ala) variant causes a missense change. The variant allele was found at a frequency of 0.479 in 1,613,942 control chromosomes in the GnomAD database, including 187,679 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.43 (14619 hom., cov: 33)
  • Exomes 𝑓: 0.48 (173060 hom.)
• Consequence: TEKT3 NM_031898.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• Publications: 32 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=0.004557818).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT3	NM_031898.3	c.845G>C	p.Gly282Ala	missense_variant	Exon 6 of 9	ENST00000395930.6	NP_114104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT3	ENST00000395930.6	c.845G>C	p.Gly282Ala	missense_variant	Exon 6 of 9	1	NM_031898.3	ENSP00000379263.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65492 AN: 151992 Hom.: 14613 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.456 AC: 114664 AN: 251388 AF XY: 0.464

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.484 AC: 706938 AN: 1461832 Hom.: 173060 Cov.: 67 AF XY: 0.485 AC XY: 352625 AN XY: 727214

African (AFR) AF: 0.311 AC: 10418 AN: 33480

American (AMR) AF: 0.394 AC: 17623 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 10365 AN: 26134

East Asian (EAS) AF: 0.413 AC: 16413 AN: 39698

South Asian (SAS) AF: 0.519 AC: 44751 AN: 86258

European-Finnish (FIN) AF: 0.503 AC: 26874 AN: 53406

Middle Eastern (MID) AF: 0.381 AC: 2199 AN: 5768

European-Non Finnish (NFE) AF: 0.495 AC: 549893 AN: 1111970

Other (OTH) AF: 0.470 AC: 28402 AN: 60396

GnomAD4 genome AF: 0.431 AC: 65524 AN: 152110 Hom.: 14619 Cov.: 33 AF XY: 0.431 AC XY: 32050 AN XY: 74356

African (AFR) AF: 0.322 AC: 13361 AN: 41510

American (AMR) AF: 0.407 AC: 6219 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2237 AN: 5160

South Asian (SAS) AF: 0.525 AC: 2529 AN: 4820

European-Finnish (FIN) AF: 0.518 AC: 5486 AN: 10592

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32924 AN: 67960

Other (OTH) AF: 0.420 AC: 888 AN: 2114

Alfa AF: 0.455 Hom.: 11970

Bravo AF: 0.416

TwinsUK AF: 0.476 AC: 1765

ALSPAC AF: 0.494 AC: 1902

ESP6500AA AF: 0.326 AC: 1437

ESP6500EA AF: 0.481 AC: 4137

ExAC AF: 0.457 AC: 55433

Asia WGS AF: 0.428 AC: 1491 AN: 3478

EpiCase AF: 0.466

EpiControl AF: 0.460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.041
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	.;T;T
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	M;M;.
PhyloP100		5.9
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.099
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.76	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.14
MPC		0.17
ClinPred		0.018	T
GERP RS		5.4
Varity_R		0.18
gMVP		0.46
Mutation Taster		=97/3	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: rs230898; hg19: chr17-15217437; COSMIC: COSV58625955; COSMIC: COSV58625955;