Variant chr16-2460346-G-C 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.90G>C(p.Gln30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,544,042 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: 0.00012 ( 0 hom. )

Consequence

TEDC2
ENST00000361837.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.370

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=0.08344525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEDC2	NM_025108.3 linkuse as main transcript	c.90G>C	p.Gln30His	missense_variant	2/10	ENST00000361837.9	NP_079384.2
TEDC2	XM_011522667.2 linkuse as main transcript	c.26+176G>C		intron_variant			XP_011520969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEDC2	ENST00000361837.9 linkuse as main transcript	c.90G>C	p.Gln30His	missense_variant	2/10	1	NM_025108.3	ENSP00000355022	P1	Q7L2K0-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000792

AC:

AN:

138922

Hom.:

AF XY:

0.0000661

AC XY:

AN XY:

75626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000215

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

165

AN:

1391828

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

686832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000228

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.000105

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000246

AC:

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

Sep 27, 2021

The c.90G>C (p.Q30H) alteration is located in exon 2 (coding exon 2) of the C16orf59 gene. This alteration results from a G to C substitution at nucleotide position 90, causing the glutamine (Q) at amino acid position 30 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.69

T;.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.072

Sift

Uncertain

0.017

D;D;.

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.90

P;.;.

Vest4

0.22

MutPred

0.16

Loss of MoRF binding (P = 0.1094);Loss of MoRF binding (P = 0.1094);Loss of MoRF binding (P = 0.1094);

MVP

0.62

MPC

0.26

ClinPred

0.23

GERP RS

-0.043

Varity_R

0.19

gMVP

0.099

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

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