Genetic Variant TRAK1:p.Glu637_Glu640del (chr3-42210085-CGGAGGAGGAGGA-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 NM_001265608.2(TRAK1):c.2084_2095delAGGAGGAGGAGG(p.Glu695_Glu698del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,577,438 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

TRAK1
NM_001265608.2 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):

developmental and epileptic encephalopathy, 68
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRAK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP3

Nonframeshift variant in repetitive region in NM_001265608.2

BS2

High AC in GnomAd4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265608.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAK1	NM_001042646.3	MANE Select	c.1963+121_1963+132delAGGAGGAGGAGG		intron	N/A	NP_001036111.1	Q9UPV9-1
TRAK1	NM_001265608.2		c.2084_2095delAGGAGGAGGAGG	p.Glu695_Glu698del	disruptive_inframe_deletion	Exon 14 of 14	NP_001252537.1
TRAK1	NM_014965.5		c.1910_1921delAGGAGGAGGAGG	p.Glu637_Glu640del	disruptive_inframe_deletion	Exon 13 of 13	NP_055780.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAK1	ENST00000341421.7	TSL:1	c.1910_1921delAGGAGGAGGAGG	p.Glu637_Glu640del	disruptive_inframe_deletion	Exon 13 of 13	ENSP00000340702.3	Q9UPV9-2
TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.1963+121_1963+132delAGGAGGAGGAGG		intron	N/A	ENSP00000328998.5	Q9UPV9-1
TRAK1	ENST00000613405.4	TSL:2	c.1862_1873delAGGAGGAGGAGG	p.Glu621_Glu624del	disruptive_inframe_deletion	Exon 13 of 13	ENSP00000483516.1	A0A087X0N0

Frequencies

GnomAD3 genomes

AF:

0.000156

AC:

AN:

147428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000676

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000414

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000225

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000158

AC:

AN:

189446

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000986

AC:

141

AN:

1429918

Hom.:

AF XY:

0.0000901

AC XY:

AN XY:

710168

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32862

American (AMR)

AF:

0.0000232

AC:

AN:

43078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24744

East Asian (EAS)

AF:

0.000282

AC:

AN:

38968

South Asian (SAS)

AF:

0.00

AC:

AN:

82464

European-Finnish (FIN)

AF:

0.000157

AC:

AN:

50806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.000101

AC:

110

AN:

1092334

Other (OTH)

AF:

0.000118

AC:

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000156

AC:

AN:

147520

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

71626

show subpopulations

African (AFR)

AF:

0.000125

AC:

AN:

40080

American (AMR)

AF:

0.0000675

AC:

AN:

14804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.000415

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:

0.000225

AC:

AN:

66788

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000497

Hom.:

317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=187/13

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-42210085-CGGAGGAGGAGGAGGA-CGGA

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