3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr3-42210085-C-CGGAGGAGGAGGAGGAGGAGGAGGA
• rs10634555
• ENST00000341421.7:c.1898_1921dupAGGAGGAGGAGGAGGAGGAGGAGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The ENST00000341421.7(TRAK1):​c.1898_1921dupAGGAGGAGGAGGAGGAGGAGGAGG​(p.Glu633_Glu640dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRAK1 ENST00000341421.7 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• 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):

• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000341421.7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.1963+109_1963+132dupAGGAGGAGGAGGAGGAGGAGGAGG		intron_variant	Intron 14 of 15	ENST00000327628.10	NP_001036111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000327628.10	c.1963+109_1963+132dupAGGAGGAGGAGGAGGAGGAGGAGG		intron_variant	Intron 14 of 15	1	NM_001042646.3	ENSP00000328998.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429916 Hom.: 0 Cov.: 0 AF XY: 0.00000282 AC XY: 2 AN XY: 710170

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32862

American (AMR) AF: 0.00 AC: 0 AN: 43078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24744

East Asian (EAS) AF: 0.00 AC: 0 AN: 38968

South Asian (SAS) AF: 0.00 AC: 0 AN: 82466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092332

Other (OTH) AF: 0.00 AC: 0 AN: 59124

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs10634555; hg19: chr3-42251577;