3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr3-42210085-C-CGGAGGAGGA
• rs10634555
• ENST00000341421.7:c.1913_1921dupAGGAGGAGG

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The ENST00000341421.7(TRAK1):​c.1913_1921dupAGGAGGAGG​(p.Glu638_Glu640dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (1 hom.)
• Consequence: TRAK1 ENST00000341421.7 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.622
• Publications: 19 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: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000341421.7
• BP6: Variant 3-42210085-C-CGGAGGAGGA is Benign according to our data. Variant chr3-42210085-C-CGGAGGAGGA is described in ClinVar as Likely_benign. ClinVar VariationId is 4083516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 560 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341421.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	NM_001042646.3	MANE Select	c.1963+124_1963+132dupAGGAGGAGG		intron	N/A	NP_001036111.1
	TRAK1	NM_001265608.2		c.2087_2095dupAGGAGGAGG	p.Glu696_Glu698dup	disruptive_inframe_insertion	Exon 14 of 14	NP_001252537.1
	TRAK1	NM_014965.5		c.1913_1921dupAGGAGGAGG	p.Glu638_Glu640dup	disruptive_inframe_insertion	Exon 13 of 13	NP_055780.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	ENST00000341421.7	TSL:1	c.1913_1921dupAGGAGGAGG	p.Glu638_Glu640dup	disruptive_inframe_insertion	Exon 13 of 13	ENSP00000340702.3
	TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.1963+124_1963+132dupAGGAGGAGG		intron	N/A	ENSP00000328998.5
	TRAK1	ENST00000613405.4	TSL:2	c.1865_1873dupAGGAGGAGG	p.Glu622_Glu624dup	disruptive_inframe_insertion	Exon 13 of 13	ENSP00000483516.1

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 561 AN: 147404 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.0123

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.00350

Gnomad FIN AF: 0.00477

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00351

GnomAD2 exomes AF: 0.00415 AC: 787 AN: 189446 AF XY: 0.00384

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00635

Gnomad ASJ exome AF: 0.00823

Gnomad EAS exome AF: 0.0162

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.00208

Gnomad OTH exome AF: 0.00400

GnomAD4 exome AF: 0.00302 AC: 4322 AN: 1429572 Hom.: 1 Cov.: 0 AF XY: 0.00302 AC XY: 2147 AN XY: 710000

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

African (AFR) AF: 0.00210 AC: 69 AN: 32856

American (AMR) AF: 0.00558 AC: 240 AN: 43046

Ashkenazi Jewish (ASJ) AF: 0.00897 AC: 222 AN: 24740

East Asian (EAS) AF: 0.0138 AC: 539 AN: 38934

South Asian (SAS) AF: 0.00426 AC: 351 AN: 82450

European-Finnish (FIN) AF: 0.00413 AC: 210 AN: 50798

Middle Eastern (MID) AF: 0.00525 AC: 29 AN: 5528

European-Non Finnish (NFE) AF: 0.00219 AC: 2389 AN: 1092104

Other (OTH) AF: 0.00462 AC: 273 AN: 59116

⚠️ 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 AF: 0.00380 AC: 560 AN: 147496 Hom.: 3 Cov.: 0 AF XY: 0.00376 AC XY: 269 AN XY: 71612

African (AFR) AF: 0.00190 AC: 76 AN: 40072

American (AMR) AF: 0.00628 AC: 93 AN: 14802

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 42 AN: 3418

East Asian (EAS) AF: 0.0164 AC: 79 AN: 4812

South Asian (SAS) AF: 0.00350 AC: 16 AN: 4566

European-Finnish (FIN) AF: 0.00477 AC: 47 AN: 9846

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.00298 AC: 199 AN: 66788

Other (OTH) AF: 0.00347 AC: 7 AN: 2016

Alfa AF: 0.00426 Hom.: 317

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRAK1: BS1

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62
Mutation Taster		=88/12	polymorphism

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;