rs6022257

Variant names:

• chr20-37990856-C-A
• rs6022257
• NM_001303457.2:c.3086+5519G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-37990856-C-A
• chr20-37990856-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001303457.2(TTI1):​c.3086+5519G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTI1 NM_001303457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTI1	NM_001303457.2	c.3086+5519G>T		intron_variant	Intron 7 of 7	ENST00000373447.8	NP_001290386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTI1	ENST00000373447.8	c.3086+5519G>T		intron_variant	Intron 7 of 7	1	NM_001303457.2	ENSP00000362546.3
TTI1	ENST00000373448.6	c.3086+5519G>T		intron_variant	Intron 8 of 8	1		ENSP00000362547.2
TTI1	ENST00000449821.1	c.3086+5519G>T		intron_variant	Intron 6 of 6	2		ENSP00000407270.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.74
DANN	Benign	0.75
PhyloP100		-0.18

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: rs6022257; hg19: chr20-36619258;