chr1-36085912-G-T

Variant names:

• chr1-36085912-G-T
• rs776242019
• NM_014466.3:c.359G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014466.3(TEKT2):​c.359G>T​(p.Arg120Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R120Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEKT2 NM_014466.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.88
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.359G>T	p.Arg120Leu	missense_variant	Exon 4 of 10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.359G>T	p.Arg120Leu	missense_variant	Exon 4 of 10		XP_005270810.1
TEKT2	XM_011541258.4	c.359G>T	p.Arg120Leu	missense_variant	Exon 4 of 10		XP_011539560.1
TEKT2	XM_017001055.2	c.359G>T	p.Arg120Leu	missense_variant	Exon 4 of 10		XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.359G>T	p.Arg120Leu	missense_variant	Exon 4 of 10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.*163G>T		non_coding_transcript_exon_variant	Exon 4 of 10	2		ENSP00000434183.1
TEKT2	ENST00000469024.1	n.*163G>T		3_prime_UTR_variant	Exon 4 of 10	2		ENSP00000434183.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		9.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.92		Loss of disorder (P = 0.053);
MVP		0.40
MPC		0.52
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.82
Mutation Taster		=34/66	disease causing

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: rs776242019; hg19: chr1-36551513;