20-38021663-A-G

Variant names:

• chr20-38021663-A-G
• rs6022419
• NM_001303457.2:c.-41-7806T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303457.2(TTI1):​c.-41-7806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,022 control chromosomes in the GnomAD database, including 13,508 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 0.41 (13508 hom., cov: 31)
• Consequence: TTI1 NM_001303457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 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.-41-7806T>C		intron	N/A	NP_001290386.1	O43156
	TTI1	NM_014657.3		c.-181-2519T>C		intron	N/A	NP_055472.1	O43156

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTI1	ENST00000373447.8	TSL:1 MANE Select	c.-41-7806T>C		intron	N/A	ENSP00000362546.3	O43156
	TTI1	ENST00000373448.6	TSL:1	c.-181-2519T>C		intron	N/A	ENSP00000362547.2	O43156
	TTI1	ENST00000898963.1		c.-41-7806T>C		intron	N/A	ENSP00000569022.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61773 AN: 151902 Hom.: 13480 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.407 AC: 61858 AN: 152022 Hom.: 13508 Cov.: 31 AF XY: 0.404 AC XY: 30017 AN XY: 74310

African (AFR) AF: 0.582 AC: 24113 AN: 41424

American (AMR) AF: 0.380 AC: 5809 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1343 AN: 3460

East Asian (EAS) AF: 0.229 AC: 1180 AN: 5162

South Asian (SAS) AF: 0.444 AC: 2138 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3135 AN: 10576

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22998 AN: 67976

Other (OTH) AF: 0.374 AC: 789 AN: 2112

Alfa AF: 0.356 Hom.: 16668

Bravo AF: 0.415

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.025
DANN	Benign	0.45
PhyloP100		-1.6
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: rs6022419; hg19: chr20-36650065;