3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGA

Variant names:

• chr3-42210085-CGGA-C
• rs10634555
• ENST00000341421.7:c.1919_1921delAGG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The ENST00000341421.7(TRAK1):​c.1919_1921delAGG​(p.Glu640del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,557,514 control chromosomes in the GnomAD database, including 11,025 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2644 hom., cov: 0)
  • Exomes 𝑓: 0.19 (8381 hom.)
• Consequence: TRAK1 ENST00000341421.7 disruptive_inframe_deletion
• Clinical Significance: 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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000341421.7
• BP6: Variant 3-42210085-CGGA-C is Benign according to our data. Variant chr3-42210085-CGGA-C is described in ClinVar as Benign. ClinVar VariationId is 3910290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.1963+130_1963+132delAGG		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+130_1963+132delAGG		intron_variant	Intron 14 of 15	1	NM_001042646.3	ENSP00000328998.5

Frequencies

GnomAD3 genomes AF: 0.189 AC: 27890 AN: 147304 Hom.: 2647 Cov.: 0

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0381

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.188 AC: 35594 AN: 189446 AF XY: 0.191

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.0449

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.189 AC: 266437 AN: 1410118 Hom.: 8381 AF XY: 0.189 AC XY: 132363 AN XY: 699364

African (AFR) AF: 0.184 AC: 5976 AN: 32402

American (AMR) AF: 0.0947 AC: 4045 AN: 42710

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4140 AN: 24204

East Asian (EAS) AF: 0.0227 AC: 884 AN: 38958

South Asian (SAS) AF: 0.172 AC: 13599 AN: 79278

European-Finnish (FIN) AF: 0.200 AC: 10014 AN: 50052

Middle Eastern (MID) AF: 0.200 AC: 1090 AN: 5462

European-Non Finnish (NFE) AF: 0.200 AC: 216214 AN: 1078914

Other (OTH) AF: 0.180 AC: 10475 AN: 58138

GnomAD4 genome AF: 0.189 AC: 27905 AN: 147396 Hom.: 2644 Cov.: 0 AF XY: 0.186 AC XY: 13339 AN XY: 71558

African (AFR) AF: 0.190 AC: 7607 AN: 40050

American (AMR) AF: 0.128 AC: 1891 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 590 AN: 3416

East Asian (EAS) AF: 0.0380 AC: 183 AN: 4816

South Asian (SAS) AF: 0.173 AC: 789 AN: 4568

European-Finnish (FIN) AF: 0.200 AC: 1970 AN: 9828

Middle Eastern (MID) AF: 0.189 AC: 54 AN: 286

European-Non Finnish (NFE) AF: 0.214 AC: 14302 AN: 66730

Other (OTH) AF: 0.183 AC: 368 AN: 2016

Alfa AF: 0.203 Hom.: 317

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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		=81/19	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: COSV58256415;