8-33500443-A-T

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

Scores

1
10
8

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.65
Variant links:
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]
MAK16 (HGNC:13703): (MAK16 homolog) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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
TTI2NM_001102401.4 linkuse as main transcriptc.1307T>A p.Ile436Asn missense_variant 7/8 ENST00000431156.7
MAK16NM_032509.4 linkuse as main transcriptc.*1814A>T 3_prime_UTR_variant 10/10 ENST00000360128.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTI2ENST00000431156.7 linkuse as main transcriptc.1307T>A p.Ile436Asn missense_variant 7/81 NM_001102401.4 P1
MAK16ENST00000360128.11 linkuse as main transcriptc.*1814A>T 3_prime_UTR_variant 10/101 NM_032509.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 providedliterature onlyOMIMNov 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
0.010
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.085
T;T;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.88
D;.;.;D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.79
D;D;D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.4
M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-2.2
.;N;N;N
REVEL
Uncertain
0.31
Sift
Benign
0.032
.;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
0.87
P;P;P;P
Vest4
0.91
MutPred
0.55
Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;
MVP
0.69
MPC
0.59
ClinPred
0.94
D
GERP RS
5.2
Varity_R
0.37
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs398122367; hg19: chr8-33357961; API