3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr3-42210085-C-CGGAGGA
• rs10634555
• ENST00000341421.7:c.1916_1921dupAGGAGG

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The ENST00000341421.7(TRAK1):​c.1916_1921dupAGGAGG​(p.Glu639_Glu640dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7034 hom., cov: 0)
  • Exomes 𝑓: 0.26 (6905 hom.)
• Consequence: TRAK1 ENST00000341421.7 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:2
• 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000341421.7
• BP6: Variant 3-42210085-C-CGGAGGA is Benign according to our data. Variant chr3-42210085-C-CGGAGGA is described in ClinVar as Benign. ClinVar VariationId is 977317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.1963+127_1963+132dupAGGAGG		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+127_1963+132dupAGGAGG		intron_variant	Intron 14 of 15	1	NM_001042646.3	ENSP00000328998.5

Frequencies

GnomAD3 genomes AF: 0.302 AC: 44489 AN: 147150 Hom.: 7029 Cov.: 0

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.319

GnomAD2 exomes AF: 0.253 AC: 47873 AN: 189446 AF XY: 0.246

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.387

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.258 AC: 367960 AN: 1426146 Hom.: 6905 Cov.: 0 AF XY: 0.258 AC XY: 182340 AN XY: 708046

African (AFR) AF: 0.231 AC: 7574 AN: 32756

American (AMR) AF: 0.397 AC: 16943 AN: 42644

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6290 AN: 24680

East Asian (EAS) AF: 0.384 AC: 14872 AN: 38736

South Asian (SAS) AF: 0.277 AC: 22707 AN: 82072

European-Finnish (FIN) AF: 0.228 AC: 11466 AN: 50332

Middle Eastern (MID) AF: 0.296 AC: 1614 AN: 5450

European-Non Finnish (NFE) AF: 0.248 AC: 270458 AN: 1090456

Other (OTH) AF: 0.272 AC: 16036 AN: 59020

GnomAD4 genome AF: 0.302 AC: 44519 AN: 147242 Hom.: 7034 Cov.: 0 AF XY: 0.306 AC XY: 21844 AN XY: 71480

African (AFR) AF: 0.259 AC: 10377 AN: 40010

American (AMR) AF: 0.441 AC: 6515 AN: 14764

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1094 AN: 3414

East Asian (EAS) AF: 0.485 AC: 2325 AN: 4792

South Asian (SAS) AF: 0.357 AC: 1628 AN: 4564

European-Finnish (FIN) AF: 0.262 AC: 2575 AN: 9814

Middle Eastern (MID) AF: 0.332 AC: 95 AN: 286

European-Non Finnish (NFE) AF: 0.286 AC: 19057 AN: 66694

Other (OTH) AF: 0.321 AC: 645 AN: 2012

Alfa AF: 0.212 Hom.: 317

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 68 Uncertain:1 Benign:1

Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jan 23, 2024

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

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

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; COSMIC: COSV58255298;