17-6812923-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]

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT1	NM_053285.2	c.760C>G	p.Arg254Gly	missense_variant	Exon 6 of 8	ENST00000338694.7	NP_444515.1
TEKT1	XM_011524027.4	c.760C>G	p.Arg254Gly	missense_variant	Exon 6 of 7		XP_011522329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT1	ENST00000338694.7	c.760C>G	p.Arg254Gly	missense_variant	Exon 6 of 8	1	NM_053285.2	ENSP00000341346.2

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 v4.3

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;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	T;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;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;