chr1-36085057-C-T

Variant names:

• chr1-36085057-C-T
• rs12043423
• NM_014466.3:c.136C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014466.3(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 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 NM_014466.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.75
• Publications: 12 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.136C>T	p.Arg46Cys	missense_variant	Exon 2 of 10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.136C>T	p.Arg46Cys	missense_variant	Exon 2 of 10		XP_005270810.1
TEKT2	XM_011541258.4	c.136C>T	p.Arg46Cys	missense_variant	Exon 2 of 10		XP_011539560.1
TEKT2	XM_017001055.2	c.136C>T	p.Arg46Cys	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.136C>T	p.Arg46Cys	missense_variant	Exon 2 of 10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.136C>T		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.0329 AC: 8260 AN: 251256 AF XY: 0.0285

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 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

African (AFR) AF: 0.0578 AC: 1934 AN: 33480

American (AMR) AF: 0.0458 AC: 2048 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.206 AC: 8198 AN: 39700

South Asian (SAS) AF: 0.00776 AC: 669 AN: 86258

European-Finnish (FIN) AF: 0.0273 AC: 1453 AN: 53306

Middle Eastern (MID) AF: 0.00988 AC: 57 AN: 5768

European-Non Finnish (NFE) AF: 0.00119 AC: 1318 AN: 1112012

Other (OTH) AF: 0.0237 AC: 1430 AN: 60396

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

African (AFR) AF: 0.0589 AC: 2448 AN: 41566

American (AMR) AF: 0.0344 AC: 527 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1207 AN: 5182

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4830

European-Finnish (FIN) AF: 0.0267 AC: 284 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00201 AC: 137 AN: 68026

Other (OTH) AF: 0.0260 AC: 55 AN: 2116

Alfa AF: 0.0153 Hom.: 562

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 25, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		4.8
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
Mutation Taster		=82/18	polymorphism (auto)

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

Other links and lift over

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