chr17-15322326-A-G

Variant names:

• chr17-15322326-A-G
• rs433068
• NM_031898.3:c.664-3179T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_031898.3(TEKT3):​c.664-3179T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 152,278 control chromosomes in the GnomAD database, including 10 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 0.0065 (10 hom., cov: 32)
• Consequence: TEKT3 NM_031898.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0065 (990/152278) while in subpopulation AFR AF = 0.022 (915/41542). AF 95% confidence interval is 0.0208. There are 10 homozygotes in GnomAd4. There are 442 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT3	NM_031898.3	c.664-3179T>C		intron_variant	Intron 4 of 8	ENST00000395930.6	NP_114104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT3	ENST00000395930.6	c.664-3179T>C		intron_variant	Intron 4 of 8	1	NM_031898.3	ENSP00000379263.1
TEKT3	ENST00000338696.6	c.664-3179T>C		intron_variant	Intron 2 of 6	1		ENSP00000343995.2
TEKT3	ENST00000539245.5	c.166-3179T>C		intron_variant	Intron 5 of 7	5		ENSP00000443280.1
TEKT3	ENST00000395931.6	n.663+5666T>C		intron_variant	Intron 3 of 7	5		ENSP00000379264.2

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 988 AN: 152160 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00650 AC: 990 AN: 152278 Hom.: 10 Cov.: 32 AF XY: 0.00594 AC XY: 442 AN XY: 74446

African (AFR) AF: 0.0220 AC: 915 AN: 41542

American (AMR) AF: 0.00385 AC: 59 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68022

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00 Hom.: 47

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism

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: rs433068; hg19: chr17-15225643;