8-33500443-A-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001102401.4(TTI2):c.1307T>A(p.Ile436Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TTI2
NM_001102401.4 missense
NM_001102401.4 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 6.65
Genes affected
TTI2 (HGNC:26262): (TELO2 interacting protein 2) This gene encodes a regulator of the DNA damage response. The protein is a component of the Triple T complex (TTT) which also includes telomere length regulation protein and TELO2 interacting protein 1. The TTT complex is involved in cellular resistance to DNA damage stresses and may act as a regulator of phosphoinositide-3-kinase-related protein kinase (PIKK) abundance. [provided by RefSeq, May 2013]
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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, 0.788
PP5
Variant 8-33500443-A-T is Pathogenic according to our data. Variant chr8-33500443-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 88868.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-33500443-A-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTI2 | NM_001102401.4 | c.1307T>A | p.Ile436Asn | missense_variant | 7/8 | ENST00000431156.7 | |
MAK16 | NM_032509.4 | c.*1814A>T | 3_prime_UTR_variant | 10/10 | ENST00000360128.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTI2 | ENST00000431156.7 | c.1307T>A | p.Ile436Asn | missense_variant | 7/8 | 1 | NM_001102401.4 | P1 | |
MAK16 | ENST00000360128.11 | c.*1814A>T | 3_prime_UTR_variant | 10/10 | 1 | NM_032509.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N;N
REVEL
Uncertain
Sift
Benign
.;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;P;P;P
Vest4
MutPred
Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;
MVP
MPC
0.59
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