17-15331578-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_031898.3(TEKT3):​c.8G>T​(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R3H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TEKT3 NM_031898.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=0.028992176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031898.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT3	NM_031898.3	MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 3 of 9	NP_114104.1	Q9BXF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT3	ENST00000395930.6	TSL:1 MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 3 of 9	ENSP00000379263.1	Q9BXF9
	TEKT3	ENST00000338696.6	TSL:1	c.8G>T	p.Arg3Leu	missense	Exon 1 of 7	ENSP00000343995.2	Q9BXF9
	TEKT3	ENST00000536146.1	TSL:4	c.8G>T	p.Arg3Leu	missense	Exon 2 of 2	ENSP00000446111.1	F5H4K1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457774 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724668

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 85974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109620

Other (OTH) AF: 0.00 AC: 0 AN: 60202

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.0080
DANN	Benign	0.24
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N
PhyloP100		0.80
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.10
Sift	Benign	0.73	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.29		Gain of helix (P = 0.0078)
MVP		0.085
MPC		0.18
ClinPred		0.073	T
GERP RS		-11
PromoterAI		0.0012	Neutral
Varity_R		0.041
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;