Genetic Variant TRAK1:p.Glu638_Glu640del (chr3-42210085-CGGAGGAGGA-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The ENST00000341421.7(TRAK1):c.1913_1921delAGGAGGAGG(p.Glu638_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 0.0000989 in 1,577,422 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

TRAK1
ENST00000341421.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRAK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000341421.7

BS2

High AC in GnomAd4 at 10 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAK1	NM_001042646.3	MANE Select	c.1963+124_1963+132delAGGAGGAGG		intron	N/A	NP_001036111.1
TRAK1	NM_001265608.2		c.2087_2095delAGGAGGAGG	p.Glu696_Glu698del	disruptive_inframe_deletion	Exon 14 of 14	NP_001252537.1
TRAK1	NM_014965.5		c.1913_1921delAGGAGGAGG	p.Glu638_Glu640del	disruptive_inframe_deletion	Exon 13 of 13	NP_055780.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAK1	ENST00000341421.7	TSL:1	c.1913_1921delAGGAGGAGG	p.Glu638_Glu640del	disruptive_inframe_deletion	Exon 13 of 13	ENSP00000340702.3
TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.1963+124_1963+132delAGGAGGAGG		intron	N/A	ENSP00000328998.5
TRAK1	ENST00000613405.4	TSL:2	c.1865_1873delAGGAGGAGG	p.Glu622_Glu624del	disruptive_inframe_deletion	Exon 13 of 13	ENSP00000483516.1

Frequencies

GnomAD3 genomes

AF:

0.0000678

AC:

AN:

147430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000749

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

146

AN:

1429900

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

710158

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32862

American (AMR)

AF:

0.0000232

AC:

AN:

43076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24744

East Asian (EAS)

AF:

0.0000513

AC:

AN:

38968

South Asian (SAS)

AF:

0.0000606

AC:

AN:

82462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50804

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.000116

AC:

127

AN:

1092322

Other (OTH)

AF:

0.000101

AC:

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000678

AC:

AN:

147522

Hom.:

Cov.:

AF XY:

0.0000558

AC XY:

AN XY:

71628

show subpopulations

African (AFR)

AF:

0.000125

AC:

AN:

40080

American (AMR)

AF:

0.00

AC:

AN:

14804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

4816

South Asian (SAS)

AF:

0.00

AC:

AN:

4568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000749

AC:

AN:

66790

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=189/11

polymorphism

(source)

Splicing

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

Publications

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3-42210085-CGGAGGAGGAGGAGGA-CGGAGGA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over