Variant chr20-37983595-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001303457.2(TTI1):c.3131T>C(p.Phe1044Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,410,988 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TTI1
NM_001303457.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

Variant links:

Genes affected

TTI1 (HGNC:29029): (TELO2 interacting protein 1) Involved in regulation of TOR signaling. Located in cytoplasm. Part of TORC1 complex and TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

TTI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTI1	NM_001303457.2 linkuse as main transcript	c.3131T>C	p.Phe1044Ser	missense_variant	8/8	ENST00000373447.8	NP_001290386.1	O43156
TTI1	NM_014657.3 linkuse as main transcript	c.3131T>C	p.Phe1044Ser	missense_variant	9/9		NP_055472.1	O43156
TTI1	XM_047440606.1 linkuse as main transcript	c.3131T>C	p.Phe1044Ser	missense_variant	8/8		XP_047296562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTI1	ENST00000373447.8 linkuse as main transcript	c.3131T>C	p.Phe1044Ser	missense_variant	8/8	1	NM_001303457.2	ENSP00000362546.3	O43156
TTI1	ENST00000373448.6 linkuse as main transcript	c.3131T>C	p.Phe1044Ser	missense_variant	9/9	1		ENSP00000362547.2	O43156
TTI1	ENST00000449821.1 linkuse as main transcript	c.3131T>C	p.Phe1044Ser	missense_variant	7/7	2		ENSP00000407270.1	O43156

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000120

AC:

AN:

1410988

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

696928

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000157

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.3131T>C (p.F1044S) alteration is located in exon 9 (coding exon 7) of the TTI1 gene. This alteration results from a T to C substitution at nucleotide position 3131, causing the phenylalanine (F) at amino acid position 1044 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;.;T

M_CAP

Benign

0.080

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.2

N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.71

P;P;P

Vest4

0.63

MutPred

0.54

Loss of catalytic residue at F1044 (P = 0.0037);Loss of catalytic residue at F1044 (P = 0.0037);Loss of catalytic residue at F1044 (P = 0.0037);

MVP

0.76

MPC

0.48

ClinPred

0.94

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over