Genetic Variant NM_001102401.4:c.980A>C (chr8-33503883-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001102401.4(TTI2):c.980A>C(p.His327Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TTI2
NM_001102401.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.840

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]

TTI2 links:

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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=0.24902102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTI2	NM_001102401.4 link	c.980A>C	p.His327Pro	missense_variant	Exon 5 of 8	ENST00000431156.7	NP_001095871.1	Q6NXR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTI2	ENST00000431156.7 link	c.980A>C	p.His327Pro	missense_variant	Exon 5 of 8	1	NM_001102401.4	ENSP00000411169.3		Q6NXR4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.015

T;T;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.67

T;.;.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

L;L;L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

.;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.15

.;T;T;T

Sift4G

Uncertain

0.033

D;D;D;D

Polyphen

0.0060

B;B;B;B

Vest4

0.43

MutPred

0.55

Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);.;

MVP

0.57

MPC

0.62

ClinPred

0.28

GERP RS

4.6

Varity_R

0.11

gMVP

0.31

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over