Variant 1-230906915-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000366661.9(TTC13):c.2573A>C(p.Lys858Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000125 in 1,503,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TTC13
ENST00000366661.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

TTC13 (HGNC:26204): (tetratricopeptide repeat domain 13)

TTC13 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=0.10879409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC13	NM_024525.5 linkuse as main transcript	c.2573A>C	p.Lys858Thr	missense_variant	23/23	ENST00000366661.9	NP_078801.3	Q8NBP0-1A0A384NPL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC13	ENST00000366661.9 linkuse as main transcript	c.2573A>C	p.Lys858Thr	missense_variant	23/23	1	NM_024525.5	ENSP00000355621.4		Q8NBP0-1
TTC13	ENST00000366662.8 linkuse as main transcript	c.2411A>C	p.Lys804Thr	missense_variant	21/21	1		ENSP00000355622.4		Q8NBP0-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000180

AC:

AN:

171908

Hom.:

AF XY:

0.000136

AC XY:

AN XY:

95688

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:

0.0000523

Gnomad NFE exome

AF:

0.000339

Gnomad OTH exome

AF:

0.000287

GnomAD4 exome

AF:

0.000124

AC:

168

AN:

1351060

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

671540

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:

0.0000398

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000131

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000233

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000181

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

Mar 24, 2023

The c.2573A>C (p.K858T) alteration is located in exon 23 (coding exon 23) of the TTC13 gene. This alteration results from a A to C substitution at nucleotide position 2573, causing the lysine (K) at amino acid position 858 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.80

P;P

Vest4

0.37

MVP

0.14

MPC

0.50

ClinPred

0.093

GERP RS

4.5

Varity_R

0.21

gMVP

0.73

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