chr1-36085075-C-T

Variant names:

• chr1-36085075-C-T
• rs149409902
• NM_014466.3:c.154C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014466.3(TEKT2):​c.154C>T​(p.Gln52*) variant causes a stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEKT2 NM_014466.3 stop_gained, splice_region
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

Genes affected

TEKT2 (HGNC:11725): (tektin 2) 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 expressed in the testis and its protein is localized to the flagella of the sperms, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.154C>T	p.Gln52*	stop_gained, splice_region_variant	Exon 2 of 10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.154C>T	p.Gln52*	stop_gained, splice_region_variant	Exon 2 of 10		XP_005270810.1
TEKT2	XM_011541258.4	c.154C>T	p.Gln52*	stop_gained, splice_region_variant	Exon 2 of 10		XP_011539560.1
TEKT2	XM_017001055.2	c.154C>T	p.Gln52*	stop_gained, splice_region_variant	Exon 2 of 10		XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.154C>T	p.Gln52*	stop_gained, splice_region_variant	Exon 2 of 10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.154C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000434183.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.8
Vest4		0.16
GERP RS		5.5
Mutation Taster		=20/180	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.050		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: rs149409902; hg19: chr1-36550676;