17-15314120-C-G

Position:

• chr17-15314120-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. 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. 13/20 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 0.43 (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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• 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/exons	MANE	UniProt
TEKT3	NM_031898.3	c.845G>C	p.Gly282Ala	missense_variant	6/9	ENST00000395930.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKT3	ENST00000395930.6	c.845G>C	p.Gly282Ala	missense_variant	6/9	1	NM_031898.3	P1
TEKT3	ENST00000338696.6	c.845G>C	p.Gly282Ala	missense_variant	4/7	1		P1
TEKT3	ENST00000539245.5	c.347G>C	p.Gly116Ala	missense_variant	7/8	5
TEKT3	ENST00000395931.6	c.*145G>C		3_prime_UTR_variant, NMD_transcript_variant	4/8	5

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

GnomAD3 exomes AF: 0.456 AC: 114664 AN: 251388 Hom.: 26716 AF XY: 0.464 AC XY: 63072 AN XY: 135876

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 SAS exome AF: 0.520

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

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.470

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

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.420

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
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	M;M;.
MutationTaster	Benign	0.13	P;P
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

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: rs230898; hg19: chr17-15217437; COSMIC: COSV58625955; COSMIC: COSV58625955;