1-36085057-C-T

Position:

• chr1-36085057-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000207457.8(TEKT2):​c.136C>T​(p.Arg46Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0135 in 1,614,098 control chromosomes in the GnomAD database, including 1,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.031 (243 hom., cov: 32)
  • Exomes 𝑓: 0.012 (1130 hom.)
• Consequence: TEKT2 ENST00000207457.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.75

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019831061).
• BP6: Variant 1-36085057-C-T is Benign according to our data. Variant chr1-36085057-C-T is described in ClinVar as [Benign]. Clinvar id is 1244486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.136C>T	p.Arg46Cys	missense_variant	2/10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.136C>T	p.Arg46Cys	missense_variant	2/10		XP_005270810.1
TEKT2	XM_011541258.4	c.136C>T	p.Arg46Cys	missense_variant	2/10		XP_011539560.1
TEKT2	XM_017001055.2	c.136C>T	p.Arg46Cys	missense_variant	2/10		XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.136C>T	p.Arg46Cys	missense_variant	2/10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.136C>T		non_coding_transcript_exon_variant	2/10	2		ENSP00000434183.1

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4710 AN: 152198 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0329 AC: 8260 AN: 251256 Hom.: 617 AF XY: 0.0285 AC XY: 3878 AN XY: 135844

Gnomad AFR exome AF: 0.0617

Gnomad AMR exome AF: 0.0456

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.240

Gnomad SAS exome AF: 0.00617

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.0212

GnomAD4 exome AF: 0.0117 AC: 17116 AN: 1461780 Hom.: 1130 Cov.: 32 AF XY: 0.0111 AC XY: 8108 AN XY: 727188

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.0458

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.00776

Gnomad4 FIN exome AF: 0.0273

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0310 AC: 4721 AN: 152318 Hom.: 243 Cov.: 32 AF XY: 0.0327 AC XY: 2438 AN XY: 74476

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0130 Hom.: 279

Bravo AF: 0.0344

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0586 AC: 258

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.0310 AC: 3761

Asia WGS AF: 0.102 AC: 355 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2021	This variant is associated with the following publications: (PMID: 26584823) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	4.5e-10	P
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.16
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.13
MPC		0.22
ClinPred		0.023	T
GERP RS		3.7
Varity_R		0.59
gMVP		0.77

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

LitVar

Other links and lift over

dbSNP: rs12043423; hg19: chr1-36550658; COSMIC: COSV52881119; COSMIC: COSV52881119;