chr20-37983632-G-A

Position:

• chr20-37983632-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303457.2(TTI1):​c.3094C>T​(p.Leu1032Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTI1 NM_001303457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25

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]

ACMG classification

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=0.19754633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTI1	NM_001303457.2	c.3094C>T	p.Leu1032Phe	missense_variant	8/8	ENST00000373447.8
TTI1	NM_014657.3	c.3094C>T	p.Leu1032Phe	missense_variant	9/9
TTI1	XM_047440606.1	c.3094C>T	p.Leu1032Phe	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTI1	ENST00000373447.8	c.3094C>T	p.Leu1032Phe	missense_variant	8/8	1	NM_001303457.2	P1
TTI1	ENST00000373448.6	c.3094C>T	p.Leu1032Phe	missense_variant	9/9	1		P1
TTI1	ENST00000449821.1	c.3094C>T	p.Leu1032Phe	missense_variant	7/7	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.3094C>T (p.L1032F) alteration is located in exon 9 (coding exon 7) of the TTI1 gene. This alteration results from a C to T substitution at nucleotide position 3094, causing the leucine (L) at amino acid position 1032 to be replaced by a phenylalanine (F). 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	Benign	0.099
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T;T
Eigen	Benign	0.030
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	.;.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.068
Sift	Uncertain	0.026	D;D;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.11
MutPred		0.33		Loss of stability (P = 0.0966);Loss of stability (P = 0.0966);Loss of stability (P = 0.0966);
MVP		0.65
MPC		0.16
ClinPred		0.89	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.094
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr20-36612034;