Variant 3-180602997-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133462.4(TTC14):c.268A>C(p.Ile90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TTC14
NM_133462.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.442

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010550618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC14	NM_133462.4 linkuse as main transcript	c.268A>C	p.Ile90Leu	missense_variant	2/12	ENST00000296015.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC14	ENST00000296015.9 linkuse as main transcript	c.268A>C	p.Ile90Leu	missense_variant	2/12	1	NM_133462.4	P1	Q96N46-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

250760

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000842

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461398

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000807

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.000132

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

Dec 20, 2023

The c.268A>C (p.I90L) alteration is located in exon 2 (coding exon 2) of the TTC14 gene. This alteration results from a A to C substitution at nucleotide position 268, causing the isoleucine (I) at amino acid position 90 to be replaced by a leucine (L). 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

0.069

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Benign

0.79

DEOGEN2

Benign

0.019

T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.50

T;T;.;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.25

N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.72

T;T;T;T

Sift4G

Benign

0.64

T;T;T;T

Polyphen

0.0020

B;.;.;B

Vest4

0.15

MutPred

0.11

Gain of glycosylation at S94 (P = 0.0535);Gain of glycosylation at S94 (P = 0.0535);Gain of glycosylation at S94 (P = 0.0535);Gain of glycosylation at S94 (P = 0.0535);

MVP

0.22

MPC

0.092

ClinPred

0.010

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.25

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