Genetic Variant TRAK1:p.Glu639_Glu640dup (chr3-42210085-C-CGGAGGA) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBA1

The NM_001265608.2(TRAK1):c.2090_2095dupAGGAGG(p.Glu697_Glu698dup) 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
NM_001265608.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.622

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001265608.2

BP6

Variant 3-42210085-C-CGGAGGA is Benign according to our data. Variant chr3-42210085-C-CGGAGGA is described in ClinVar as [Benign]. Clinvar id is 977317.Status of the report is criteria_provided_single_submitter, 1 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 link	c.1963+127_1963+132dupAGGAGG		intron_variant	Intron 14 of 15	ENST00000327628.10	NP_001036111.1	Q9UPV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000327628.10 link	c.1963+127_1963+132dupAGGAGG		intron_variant	Intron 14 of 15	1	NM_001042646.3	ENSP00000328998.5		Q9UPV9-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

44489

AN:

147150

Hom.:

7029

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.253

AC:

47873

AN:

189446

Hom.:

1448

AF XY:

0.246

AC XY:

25246

AN XY:

102570

show subpopulations

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 SAS exome

AF:

0.239

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.:

AF XY:

0.258

AC XY:

182340

AN XY:

708046

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.302

AC:

44519

AN:

147242

Hom.:

7034

Cov.:

AF XY:

0.306

AC XY:

21844

AN XY:

71480

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.485

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.321

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 68

Uncertain:1Benign:1

Jan 23, 2024

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGAGGA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over