chr5-40728377-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_012382.3(TTC33):c.403C>T(p.Arg135Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,457,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
TTC33
NM_012382.3 missense
NM_012382.3 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 9.20
Genes affected
TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.859
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC33 | NM_012382.3 | c.403C>T | p.Arg135Cys | missense_variant | 4/5 | ENST00000337702.5 | |
TTC33 | XM_011514003.4 | c.403C>T | p.Arg135Cys | missense_variant | 4/5 | ||
PTGER4 | XM_017009659.3 | c.*38-12107G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC33 | ENST00000337702.5 | c.403C>T | p.Arg135Cys | missense_variant | 4/5 | 1 | NM_012382.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251162Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135760
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1457488Hom.: 0 Cov.: 33 AF XY: 0.0000290 AC XY: 21AN XY: 725086
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
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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 13, 2021 | The c.403C>T (p.R135C) alteration is located in exon 4 (coding exon 3) of the TTC33 gene. This alteration results from a C to T substitution at nucleotide position 403, causing the arginine (R) at amino acid position 135 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0307);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at