3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGA

Position:

• chr3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGA

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The ENST00000341421.7(TRAK1):​c.1919_1921dup​(p.Glu640dup) variant causes a 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 ENST00000341421.7 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.622

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000341421.7
• BP6: Variant 3-42210085-C-CGGA is Benign according to our data. Variant chr3-42210085-C-CGGA is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.1963+130_1963+132dup		intron_variant		ENST00000327628.10	NP_001036111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000327628.10	c.1963+130_1963+132dup		intron_variant		1	NM_001042646.3	ENSP00000328998	P1

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

GnomAD3 exomes AF: 0.274 AC: 51993 AN: 189446 Hom.: 768 AF XY: 0.266 AC XY: 27304 AN XY: 102570

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 SAS exome AF: 0.176

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

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.251

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

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.282

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10634555; hg19: chr3-42251577;