3-42210085-CGGAGGAGGAGGAGGA-CGGAGGA

Variant names:

• chr3-42210089-GGAGGAGGAG-GG
• ENST00000341421.7:c.1895_1902delAGGAGGAG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001265608.2(TRAK1):​c.2069_2076delAGGAGGAG​(p.Glu690GlyfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRAK1 NM_001265608.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

TRAK1 (HGNC:29947): (trafficking kinesin protein 1) Predicted to enable GABA receptor binding activity and myosin binding activity. Involved in endosome to lysosome transport. Located in early endosome and mitochondrion. Implicated in developmental and epileptic encephalopathy 68. [provided by Alliance of Genome Resources, Apr 2022]

TRAK1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 68

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0743 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265608.2. 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
	TRAK1	NM_001042646.3	MANE Select	c.1963+106_1963+113delAGGAGGAG		intron	N/A	NP_001036111.1	Q9UPV9-1
	TRAK1	NM_001265608.2		c.2069_2076delAGGAGGAG	p.Glu690GlyfsTer10	frameshift	Exon 14 of 14	NP_001252537.1
	TRAK1	NM_014965.5		c.1895_1902delAGGAGGAG	p.Glu632GlyfsTer10	frameshift	Exon 13 of 13	NP_055780.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	ENST00000341421.7	TSL:1	c.1895_1902delAGGAGGAG	p.Glu632GlyfsTer10	frameshift	Exon 13 of 13	ENSP00000340702.3	Q9UPV9-2
	TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.1963+106_1963+113delAGGAGGAG		intron	N/A	ENSP00000328998.5	Q9UPV9-1
	TRAK1	ENST00000613405.4	TSL:2	c.1847_1854delAGGAGGAG	p.Glu616GlyfsTer10	frameshift	Exon 13 of 13	ENSP00000483516.1	A0A087X0N0

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

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: chr3-42251581;