1-36085993-C-G

Position:

• chr1-36085993-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014466.3(TEKT2):​c.440C>G​(p.Thr147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEKT2 NM_014466.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13643247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.440C>G	p.Thr147Ser	missense_variant	4/10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.440C>G	p.Thr147Ser	missense_variant	4/10		XP_005270810.1
TEKT2	XM_011541258.4	c.440C>G	p.Thr147Ser	missense_variant	4/10		XP_011539560.1
TEKT2	XM_017001055.2	c.440C>G	p.Thr147Ser	missense_variant	4/10		XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.440C>G	p.Thr147Ser	missense_variant	4/10	1	NM_014466.3	ENSP00000207457	P1
TEKT2	ENST00000469024.1	c.*244C>G		3_prime_UTR_variant, NMD_transcript_variant	4/10	2		ENSP00000434183

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.440C>G (p.T147S) alteration is located in exon 4 (coding exon 3) of the TEKT2 gene. This alteration results from a C to G substitution at nucleotide position 440, causing the threonine (T) at amino acid position 147 to be replaced by a serine (S). 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	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.059
Sift	Benign	0.22	T
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.65		Loss of stability (P = 0.0717);
MVP		0.076
MPC		0.079
ClinPred		0.23	T
GERP RS		3.6
Varity_R		0.11
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-36551594;