3-180604878-C-A

Variant summary

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

The NM_133462.4(TTC14):​c.728C>A​(p.Ser243Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

TTC14
NM_133462.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89
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]
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]

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=0.2639379).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC14NM_133462.4 linkc.728C>A p.Ser243Tyr missense_variant Exon 6 of 12 ENST00000296015.9 NP_597719.1 Q96N46-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTC14ENST00000296015.9 linkc.728C>A p.Ser243Tyr missense_variant Exon 6 of 12 1 NM_133462.4 ENSP00000296015.4 Q96N46-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152028
Hom.:
0
Cov.:
33
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249536
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135170
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:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000486
AC:
71
AN:
1460540
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
726620
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:
0.00
Gnomad4 NFE exome
AF:
0.0000630
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152028
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74260
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000807
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.728C>A (p.S243Y) alteration is located in exon 6 (coding exon 6) of the TTC14 gene. This alteration results from a C to A substitution at nucleotide position 728, causing the serine (S) at amino acid position 243 to be replaced by a tyrosine (Y). 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
0.13
BayesDel_addAF
Uncertain
0.018
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.85
D;.;D;D
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.5
L;L;L;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.5
N;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.029
D;D;D;D
Sift4G
Uncertain
0.041
D;T;D;D
Polyphen
0.94
P;.;D;.
Vest4
0.61
MutPred
0.34
Gain of glycosylation at Y247 (P = 0.0138);Gain of glycosylation at Y247 (P = 0.0138);Gain of glycosylation at Y247 (P = 0.0138);.;
MVP
0.67
MPC
0.46
ClinPred
0.86
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs761414878; hg19: chr3-180322666; API