Variant 16-10635882-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144674.2(TEKT5):c.1123A>C(p.Met375Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000966 in 1,614,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000094 ( 1 hom. )

Consequence

TEKT5
NM_144674.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.390

Variant links:

Genes affected

TEKT5 (HGNC:26554): (tektin 5) Predicted to be involved in cilium assembly and cilium movement involved in cell motility. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TEKT5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023847938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKT5	NM_144674.2 linkuse as main transcript	c.1123A>C	p.Met375Leu	missense_variant	6/7	ENST00000283025.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TEKT5	ENST00000283025.7 linkuse as main transcript	c.1123A>C	p.Met375Leu	missense_variant	6/7	1	NM_144674.2	P1
TEKT5	ENST00000576638.1 linkuse as main transcript	c.442A>C	p.Met148Leu	missense_variant	5/5	3
TEKT5	ENST00000574923.1 linkuse as main transcript	n.106A>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000187

AC:

AN:

251360

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000118

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000253

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2022

The c.1123A>C (p.M375L) alteration is located in exon 6 (coding exon 6) of the TEKT5 gene. This alteration results from a A to C substitution at nucleotide position 1123, causing the methionine (M) at amino acid position 375 to be replaced by a leucine (L). 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

0.069

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.68

DEOGEN2

Benign

0.0067

T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.13

Sift

Benign

0.086

T;.

Sift4G

Benign

0.23

T;.

Polyphen

0.0010

B;.

Vest4

0.33

MutPred

0.48

Loss of disorder (P = 0.1311);.;

MVP

0.24

MPC

0.024

ClinPred

0.033

GERP RS

0.80

Varity_R

0.16

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over