Variant chr1-51290556-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001297663.2(TTC39A):c.1336G>C(p.Glu446Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,613,994 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

TTC39A
NM_001297663.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.750

Variant links:

Genes affected

TTC39A (HGNC:18657): (tetratricopeptide repeat domain 39A) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

TTC39A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061426163).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC39A	NM_001297663.2 linkuse as main transcript	c.1336G>C	p.Glu446Gln	missense_variant	15/18	ENST00000680483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39A	ENST00000680483.1 linkuse as main transcript	c.1336G>C	p.Glu446Gln	missense_variant	15/18		NM_001297663.2	A1	Q5SRH9-5

Frequencies

GnomAD3 genomes

AF:

0.000926

AC:

141

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00104

AC:

259

AN:

248946

Hom.:

AF XY:

0.00110

AC XY:

149

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00122

AC:

1778

AN:

1461622

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

846

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00176

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000919

AC:

140

AN:

152372

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000748

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00121

AC:

ExAC

AF:

0.00111

AC:

134

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 06, 2023

The c.1348G>C (p.E450Q) alteration is located in exon 15 (coding exon 15) of the TTC39A gene. This alteration results from a G to C substitution at nucleotide position 1348, causing the glutamic acid (E) at amino acid position 450 to be replaced by a glutamine (Q). 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

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.17

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.64

T;T;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0061

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.55

N;N;N;N;N;N

REVEL

Benign

0.073

Sift

Benign

0.54

T;T;T;T;T;T

Sift4G

Benign

0.56

T;T;T;T;T;.

Polyphen

0.0010, 0.0, 0.0050

.;B;B;B;.;.

Vest4

0.071

MVP

0.16

MPC

0.36

ClinPred

0.0089

GERP RS

4.5

Varity_R

0.054

gMVP

0.26

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