chr17-17862820-GG-TA

Variant names:

• chr17-17862820-GG-TA
• NM_001082968.2:c.1112_1113delCCinsTA
• TOM1L2 p.Thr371Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001082968.2(TOM1L2):​c.1112_1113delCCinsTA​(p.Thr371Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T371N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOM1L2 NM_001082968.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.12
• Publications: 0 publications found

Genes affected

TOM1L2 (HGNC:11984): (target of myb1 like 2 membrane trafficking protein) This gene belongs to a small gene family whose members have an N-terminal VHS domain followed by a GAT domain; domains which typically participate in vesicular trafficking. The canonical protein encoded by this gene also has a C-terminal clathrin binding motif. This protein has been shown to interact with Tollip, clathrin and ubiquitin and is thought to play a role in endosomal sorting. This gene resides in the 3.7 Mb deletion of chromosome region 17p11.2 that is associated with Smith-Magenis syndrome. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Apr 2017]

ENSG00000301763 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082968.2. 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
	TOM1L2	NM_001082968.2	MANE Select	c.1112_1113delCCinsTA	p.Thr371Ile	missense	N/A	NP_001076437.1	Q6ZVM7-1
	TOM1L2	NM_001350332.2		c.1112_1113delCCinsTA	p.Thr371Ile	missense	N/A	NP_001337261.1
	TOM1L2	NM_001350333.2		c.1112_1113delCCinsTA	p.Thr371Ile	missense	N/A	NP_001337262.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1L2	ENST00000379504.8	TSL:2 MANE Select	c.1112_1113delCCinsTA	p.Thr371Ile	missense	N/A	ENSP00000368818.3	Q6ZVM7-1
	TOM1L2	ENST00000581396.6	TSL:1	c.962_963delCCinsTA	p.Thr321Ile	missense	N/A	ENSP00000464297.1	Q6ZVM7-2
	TOM1L2	ENST00000890541.1		c.1280_1281delCCinsTA	p.Thr427Ile	missense	N/A	ENSP00000560600.1

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-17766134;