20-37983482-G-A

Position:

• chr20-37983482-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.3244C>T​(p.Leu1082Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTI1 NM_001303457.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20

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=0.0856677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTI1	NM_001303457.2	c.3244C>T	p.Leu1082Phe	missense_variant	8/8	ENST00000373447.8
TTI1	NM_014657.3	c.3244C>T	p.Leu1082Phe	missense_variant	9/9
TTI1	XM_047440606.1	c.3244C>T	p.Leu1082Phe	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTI1	ENST00000373447.8	c.3244C>T	p.Leu1082Phe	missense_variant	8/8	1	NM_001303457.2	P1
TTI1	ENST00000373448.6	c.3244C>T	p.Leu1082Phe	missense_variant	9/9	1		P1
TTI1	ENST00000449821.1	c.3244C>T	p.Leu1082Phe	missense_variant	7/7	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	.;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.90	N;N;N
REVEL	Benign	0.077
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.098	T;T;T
Polyphen		0.072	B;B;B
Vest4		0.37
MutPred		0.33		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.24
MPC		0.21
ClinPred		0.18	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.20

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

Other links and lift over

dbSNP: rs2073148610; hg19: chr20-36611884;