rs399393

Variant names:

• chr1-36088072-A-G
• rs399393
• NM_014466.3:c.1179A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014466.3(TEKT2):​c.1179A>G​(p.Thr393Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,612,964 control chromosomes in the GnomAD database, including 686,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64981 hom., cov: 33)
  • Exomes 𝑓: 0.92 (621535 hom.)
• Consequence: TEKT2 NM_014466.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.78
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-36088072-A-G is Benign according to our data. Variant chr1-36088072-A-G is described in ClinVar as Benign. ClinVar VariationId is 1180264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.1179A>G	p.Thr393Thr	synonymous_variant	Exon 10 of 10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.1179A>G	p.Thr393Thr	synonymous_variant	Exon 10 of 10		XP_005270810.1
TEKT2	XM_011541258.4	c.1179A>G	p.Thr393Thr	synonymous_variant	Exon 10 of 10		XP_011539560.1
TEKT2	XM_017001055.2	c.1179A>G	p.Thr393Thr	synonymous_variant	Exon 10 of 10		XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.1179A>G	p.Thr393Thr	synonymous_variant	Exon 10 of 10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.*983A>G		non_coding_transcript_exon_variant	Exon 10 of 10	2		ENSP00000434183.1
TEKT2	ENST00000473120.1	c.*261A>G		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000432793.1
TEKT2	ENST00000469024.1	n.*983A>G		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000434183.1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140466 AN: 152152 Hom.: 64924 Cov.: 33

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.919

GnomAD2 exomes AF: 0.927 AC: 231707 AN: 249926 AF XY: 0.925

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.904

Gnomad NFE exome AF: 0.916

Gnomad OTH exome AF: 0.926

GnomAD4 exome AF: 0.922 AC: 1347205 AN: 1460694 Hom.: 621535 Cov.: 74 AF XY: 0.922 AC XY: 669620 AN XY: 726618

African (AFR) AF: 0.918 AC: 30727 AN: 33474

American (AMR) AF: 0.960 AC: 42889 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 23547 AN: 26130

East Asian (EAS) AF: 1.00 AC: 39687 AN: 39694

South Asian (SAS) AF: 0.913 AC: 78717 AN: 86202

European-Finnish (FIN) AF: 0.904 AC: 47490 AN: 52510

Middle Eastern (MID) AF: 0.903 AC: 5195 AN: 5756

European-Non Finnish (NFE) AF: 0.920 AC: 1023219 AN: 1111868

Other (OTH) AF: 0.923 AC: 55734 AN: 60374

GnomAD4 genome AF: 0.923 AC: 140581 AN: 152270 Hom.: 64981 Cov.: 33 AF XY: 0.923 AC XY: 68743 AN XY: 74444

African (AFR) AF: 0.919 AC: 38213 AN: 41566

American (AMR) AF: 0.945 AC: 14458 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3105 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5147 AN: 5152

South Asian (SAS) AF: 0.919 AC: 4433 AN: 4826

European-Finnish (FIN) AF: 0.900 AC: 9553 AN: 10614

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62581 AN: 68020

Other (OTH) AF: 0.921 AC: 1946 AN: 2114

Alfa AF: 0.920 Hom.: 101696

Bravo AF: 0.925

Asia WGS AF: 0.969 AC: 3369 AN: 3478

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

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.52
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs399393; hg19: chr1-36553673; COSMIC: COSV108025443; COSMIC: COSV108025443;