chr21-37121904-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001330683.2(TTC3):c.988A>G(p.Lys330Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TTC3
NM_001330683.2 missense
NM_001330683.2 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 3.27
Genes affected
TTC3 (HGNC:12393): (tetratricopeptide repeat domain 3) Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28153723).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC3 | NM_001330683.2 | c.988A>G | p.Lys330Glu | missense_variant | 12/46 | ENST00000418766.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC3 | ENST00000418766.6 | c.988A>G | p.Lys330Glu | missense_variant | 12/46 | 5 | NM_001330683.2 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Jul 20, 2022 | The c.988A>G (p.K330E) alteration is located in exon 12 (coding exon 11) of the TTC3 gene. This alteration results from a A to G substitution at nucleotide position 988, causing the lysine (K) at amino acid position 330 to be replaced by a glutamic acid (E). 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
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
1.0, 0.89
.;.;.;D;P;D;D
Vest4
0.48, 0.33, 0.47, 0.50
MutPred
Loss of methylation at K330 (P = 0.0021);Loss of methylation at K330 (P = 0.0021);.;Loss of methylation at K330 (P = 0.0021);.;Loss of methylation at K330 (P = 0.0021);Loss of methylation at K330 (P = 0.0021);
MVP
MPC
0.34
ClinPred
D
GERP RS
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