5-160010815-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003314.3(TTC1):c.287A>G(p.Tyr96Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,242 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
TTC1
NM_003314.3 missense
NM_003314.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.77
Genes affected
TTC1 (HGNC:12391): (tetratricopeptide repeat domain 1) This gene encodes a protein that belongs to the tetratrico peptide repeat superfamily of proteins. The encoded protein plays a role in protein-protein interactions, and binds to the Galpha subunit of G protein-coupled receptors to activate the Ras signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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=0.13847023).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC1 | NM_003314.3 | c.287A>G | p.Tyr96Cys | missense_variant | 2/8 | ENST00000231238.10 | |
TTC1 | NM_001282500.2 | c.287A>G | p.Tyr96Cys | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC1 | ENST00000231238.10 | c.287A>G | p.Tyr96Cys | missense_variant | 2/8 | 1 | NM_003314.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152226Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
152226
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000803 AC: 20AN: 248980Hom.: 0 AF XY: 0.0000742 AC XY: 10AN XY: 134842
GnomAD3 exomes
AF:
AC:
20
AN:
248980
Hom.:
AF XY:
AC XY:
10
AN XY:
134842
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461016Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 726680
GnomAD4 exome
AF:
AC:
59
AN:
1461016
Hom.:
Cov.:
31
AF XY:
AC XY:
28
AN XY:
726680
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74370
GnomAD4 genome
?
AF:
AC:
6
AN:
152226
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74370
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
6
EpiCase
AF:
EpiControl
AF:
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 | Apr 20, 2023 | The c.287A>G (p.Y96C) alteration is located in exon 2 (coding exon 1) of the TTC1 gene. This alteration results from a A to G substitution at nucleotide position 287, causing the tyrosine (Y) at amino acid position 96 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of phosphorylation at Y96 (P = 0.0059);Loss of phosphorylation at Y96 (P = 0.0059);
MVP
MPC
0.41
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at