Genetic Variant NM_014466.3:c.306C>G (chr1-36085859-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014466.3(TEKT2):c.306C>G(p.Asn102Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,844 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

TEKT2
NM_014466.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401

Publications

0 publications found

Variant links:

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]

TEKT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040720254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3 link	c.306C>G	p.Asn102Lys	missense_variant	Exon 4 of 10	ENST00000207457.8	NP_055281.2	Q9UIF3
TEKT2	XM_005270753.3 link	c.306C>G	p.Asn102Lys	missense_variant	Exon 4 of 10		XP_005270810.1	Q9UIF3
TEKT2	XM_011541258.4 link	c.306C>G	p.Asn102Lys	missense_variant	Exon 4 of 10		XP_011539560.1	Q9UIF3
TEKT2	XM_017001055.2 link	c.306C>G	p.Asn102Lys	missense_variant	Exon 4 of 10		XP_016856544.1	Q9UIF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEKT2	ENST00000207457.8 link	c.306C>G	p.Asn102Lys	missense_variant	Exon 4 of 10	1	NM_014466.3	ENSP00000207457.3	Q9UIF3
TEKT2	ENST00000469024.1 link	n.*110C>G		non_coding_transcript_exon_variant	Exon 4 of 10	2		ENSP00000434183.1	E9PRS9
TEKT2	ENST00000469024.1 link	n.*110C>G		3_prime_UTR_variant	Exon 4 of 10	2		ENSP00000434183.1	E9PRS9

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000160

AC:

AN:

249802

AF XY:

0.000214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000762

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.0000862

AC:

126

AN:

1461586

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.000353

AC:

AN:

39700

South Asian (SAS)

AF:

0.000940

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111926

Other (OTH)

AF:

0.000447

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000105

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41546

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00154

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 31, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.306C>G (p.N102K) 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 306, causing the asparagine (N) at amino acid position 102 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

Benign

0.26

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.050

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

M_CAP

Benign

0.0086

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PhyloP100

0.40

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.22

REVEL

Benign

0.077

Sift

Benign

0.12

Sift4G

Benign

0.44

Polyphen

0.067

Vest4

0.44

MutPred

0.66

Gain of ubiquitination at N102 (P = 0.017);

MVP

0.18

MPC

0.11

ClinPred

0.033

GERP RS

3.9

Varity_R

0.19

gMVP

0.55

Mutation Taster

=72/28

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_014466.3:c.306C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over