chr1-36085062-C-G

Variant names:

• chr1-36085062-C-G
• NM_014466.3:c.141C>G

Variant summary

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

The NM_014466.3(TEKT2):​c.141C>G​(p.Asn47Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEKT2 NM_014466.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.396
• 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 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
TEKT2	NM_014466.3	c.141C>G	p.Asn47Lys	missense_variant	Exon 2 of 10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.141C>G	p.Asn47Lys	missense_variant	Exon 2 of 10		XP_005270810.1
TEKT2	XM_011541258.4	c.141C>G	p.Asn47Lys	missense_variant	Exon 2 of 10		XP_011539560.1
TEKT2	XM_017001055.2	c.141C>G	p.Asn47Lys	missense_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.141C>G	p.Asn47Lys	missense_variant	Exon 2 of 10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.141C>G		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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.141C>G (p.N47K) alteration is located in exon 2 (coding exon 1) of the TEKT2 gene. This alteration results from a C to G substitution at nucleotide position 141, causing the asparagine (N) at amino acid position 47 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.40
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.020	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.52		Gain of ubiquitination at N47 (P = 0.0128);
MVP		0.099
MPC		0.50
ClinPred		1.0	D
GERP RS		-7.4
Varity_R		0.79
gMVP		0.72
Mutation Taster		=38/62	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

hg19: chr1-36550663;