chr20-37991079-C-T

Variant names:

• chr20-37991079-C-T
• rs6022259
• NM_001303457.2:c.3086+5296G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001303457.2(TTI1):​c.3086+5296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,098 control chromosomes in the GnomAD database, including 7,834 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7834 hom., cov: 33)
• Consequence: TTI1 NM_001303457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly and movement abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Broad Center for Mendelian Genomics
• microcephaly

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303457.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTI1	NM_001303457.2	MANE Select	c.3086+5296G>A		intron	N/A	NP_001290386.1
	TTI1	NM_014657.3		c.3086+5296G>A		intron	N/A	NP_055472.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTI1	ENST00000373447.8	TSL:1 MANE Select	c.3086+5296G>A		intron	N/A	ENSP00000362546.3
	TTI1	ENST00000373448.6	TSL:1	c.3086+5296G>A		intron	N/A	ENSP00000362547.2
	TTI1	ENST00000898963.1		c.3140+5296G>A		intron	N/A	ENSP00000569022.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42797 AN: 151978 Hom.: 7812 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 42879 AN: 152098 Hom.: 7834 Cov.: 33 AF XY: 0.280 AC XY: 20795 AN XY: 74354

African (AFR) AF: 0.531 AC: 22016 AN: 41454

American (AMR) AF: 0.189 AC: 2889 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1060 AN: 5186

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1647 AN: 10564

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12415 AN: 68004

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.219 Hom.: 12221

Bravo AF: 0.289

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6022259; hg19: chr20-36619481;