Variant 16-2464618-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000361837.9(TEDC2):c.1252G>A(p.Glu418Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,612,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

TEDC2
ENST00000361837.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.945

Variant links:

Genes affected

TEDC2 (HGNC:25849): (tubulin epsilon and delta complex 2) Predicted to be involved in positive regulation of smoothened signaling pathway. Predicted to be located in centriole and cilium. [provided by Alliance of Genome Resources, Apr 2022]

TEDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08873394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEDC2	NM_025108.3 linkuse as main transcript	c.1252G>A	p.Glu418Lys	missense_variant	10/10	ENST00000361837.9	NP_079384.2
TEDC2	XM_011522667.2 linkuse as main transcript	c.1153G>A	p.Glu385Lys	missense_variant	9/9		XP_011520969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEDC2	ENST00000361837.9 linkuse as main transcript	c.1252G>A	p.Glu418Lys	missense_variant	10/10	1	NM_025108.3	ENSP00000355022	P1	Q7L2K0-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

246478

Hom.:

AF XY:

0.000201

AC XY:

AN XY:

134340

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000285

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.000173

AC:

253

AN:

1460224

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

726414

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000231

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000112

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000302

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000190

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Nov 12, 2021

The c.1252G>A (p.E418K) alteration is located in exon 10 (coding exon 10) of the C16orf59 gene. This alteration results from a G to A substitution at nucleotide position 1252, causing the glutamic acid (E) at amino acid position 418 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

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.11

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.99

D;.

Vest4

0.42

MVP

0.66

MPC

0.57

ClinPred

0.063

GERP RS

2.4

Varity_R

0.21

gMVP

0.50

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