chr17-6812923-G-C

Variant names:

• chr17-6812923-G-C
• rs3744395
• NM_053285.2:c.760C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_053285.2(TEKT1):​c.760C>G​(p.Arg254Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R254H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEKT1 NM_053285.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974
• Publications: 30 publications found

Genes affected

TEKT1 (HGNC:15534): (tektin 1) 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. This gene is predominantly expressed in the testis and in mouse, tektin 1 mRNA was localized to the spermatocytes and round spermatids in the seminiferous tubules, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

TEKT1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053285.2. 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
	TEKT1	NM_053285.2	MANE Select	c.760C>G	p.Arg254Gly	missense	Exon 6 of 8	NP_444515.1	Q969V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT1	ENST00000338694.7	TSL:1 MANE Select	c.760C>G	p.Arg254Gly	missense	Exon 6 of 8	ENSP00000341346.2	Q969V4
	TEKT1	ENST00000572291.1	TSL:5	c.145C>G	p.Arg49Gly	missense	Exon 2 of 3	ENSP00000458518.1	I3L122
	TEKT1	ENST00000571744.1	TSL:3	c.94C>G	p.Arg32Gly	missense	Exon 1 of 2	ENSP00000460197.2	I3L357

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 16815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.97
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.14
Sift	Benign	0.064	T
Sift4G	Benign	0.12	T
Polyphen		0.18	B
Vest4		0.58
MutPred		0.54		Gain of ubiquitination at K255 (P = 0.0598)
MVP		0.21
MPC		0.25
ClinPred		0.92	D
GERP RS		0.21
PromoterAI		-0.058	Neutral
Varity_R		0.51
gMVP		0.53

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: rs3744395; hg19: chr17-6716242;