Variant 3-180609742-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_133462.4(TTC14):c.1513C>T(p.His505Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,830 control chromosomes in the GnomAD database, including 4 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H505R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 3 hom. )

Consequence

TTC14
NM_133462.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TTC14 links:

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

CCDC39 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010725021).

BP6

Variant 3-180609742-C-T is Benign according to our data. Variant chr3-180609742-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045653.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC14	NM_133462.4 linkuse as main transcript	c.1513C>T	p.His505Tyr	missense_variant	12/12	ENST00000296015.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC14	ENST00000296015.9 linkuse as main transcript	c.1513C>T	p.His505Tyr	missense_variant	12/12	1	NM_133462.4	P1	Q96N46-1

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00274

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00147

AC:

368

AN:

251074

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00224

AC:

3270

AN:

1461620

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1594

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00262

Gnomad4 NFE exome

AF:

0.00270

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152210

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00274

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00161

AC:

195

EpiCase

AF:

0.00240

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TTC14-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

-0.022

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.21

Sift

Benign

0.057

T;T

Sift4G

Uncertain

0.027

D;T

Polyphen

0.052

B;P

Vest4

0.17

MVP

0.93

MPC

0.10

ClinPred

0.014

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.11

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