3-42210085-C-CGGA

Variant names:

• chr3-42210085-C-CGGA
• rs10634555
• ENST00000341421.7:c.1919_1921dupAGG

Variant summary

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

The NM_001265608.2(TRAK1):​c.2093_2095dupAGG​(p.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 0.28 (5962 hom., cov: 0)
  • Exomes 𝑓: 0.25 (7298 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAK1 NM_001265608.2 disruptive_inframe_insertion
• 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):

• 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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001265608.2
• BP6: Variant 3-42210085-C-CGGA is Benign according to our data. Variant chr3-42210085-C-CGGA is described in ClinVar as Benign. ClinVar VariationId is 1260505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	NM_001042646.3	MANE Select	c.1963+130_1963+132dupAGG		intron	N/A	NP_001036111.1	Q9UPV9-1
	TRAK1	NM_001265608.2		c.2093_2095dupAGG	p.Glu698dup	disruptive_inframe_insertion	Exon 14 of 14	NP_001252537.1
	TRAK1	NM_014965.5		c.1919_1921dupAGG	p.Glu640dup	disruptive_inframe_insertion	Exon 13 of 13	NP_055780.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	ENST00000341421.7	TSL:1	c.1919_1921dupAGG	p.Glu640dup	disruptive_inframe_insertion	Exon 13 of 13	ENSP00000340702.3	Q9UPV9-2
	TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.1963+130_1963+132dupAGG		intron	N/A	ENSP00000328998.5	Q9UPV9-1
	TRAK1	ENST00000613405.4	TSL:2	c.1871_1873dupAGG	p.Glu624dup	disruptive_inframe_insertion	Exon 13 of 13	ENSP00000483516.1	A0A087X0N0

Frequencies

GnomAD3 genomes AF: 0.281 AC: 41281 AN: 147080 Hom.: 5960 Cov.: 0

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.274 AC: 51993 AN: 189446 AF XY: 0.266

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.266

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.246 AC: 327382 AN: 1329102 Hom.: 7298 Cov.: 0 AF XY: 0.244 AC XY: 161269 AN XY: 660148

African (AFR) AF: 0.294 AC: 9184 AN: 31264

American (AMR) AF: 0.304 AC: 10751 AN: 35394

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5233 AN: 22856

East Asian (EAS) AF: 0.471 AC: 14564 AN: 30898

South Asian (SAS) AF: 0.179 AC: 13328 AN: 74632

European-Finnish (FIN) AF: 0.306 AC: 14733 AN: 48110

Middle Eastern (MID) AF: 0.225 AC: 1157 AN: 5140

European-Non Finnish (NFE) AF: 0.238 AC: 244713 AN: 1026226

Other (OTH) AF: 0.251 AC: 13719 AN: 54582

GnomAD4 genome AF: 0.281 AC: 41311 AN: 147170 Hom.: 5962 Cov.: 0 AF XY: 0.281 AC XY: 20091 AN XY: 71434

African (AFR) AF: 0.323 AC: 12936 AN: 39992

American (AMR) AF: 0.246 AC: 3629 AN: 14752

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 805 AN: 3418

East Asian (EAS) AF: 0.439 AC: 2101 AN: 4790

South Asian (SAS) AF: 0.171 AC: 779 AN: 4558

European-Finnish (FIN) AF: 0.355 AC: 3468 AN: 9768

Middle Eastern (MID) AF: 0.213 AC: 60 AN: 282

European-Non Finnish (NFE) AF: 0.253 AC: 16868 AN: 66708

Other (OTH) AF: 0.282 AC: 566 AN: 2010

Alfa AF: 0.248 Hom.: 317

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10634555; hg19: chr3-42251577; COSMIC: COSV58255681;