3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGA

Position:

• chr3-42210085-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The ENST00000327628.10(TRAK1):​c.1963+130_1963+132del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,557,514 control chromosomes in the GnomAD database, including 11,025 homozygotes. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (2644 hom., cov: 0)
  • Exomes 𝑓: 0.19 (8381 hom.)
• Consequence: TRAK1 ENST00000327628.10 intron
• Clinical Significance: Not reported in ClinVar
• 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 -9 ACMG points.

• BP6: Variant 3-42210085-CGGA-C is Benign according to our data. Variant chr3-42210085-CGGA-C is described in Lovd as [Likely_benign]. Variant chr3-42210085-CGGA-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 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+132del		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+132del		intron_variant		1	NM_001042646.3	ENSP00000328998	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 27890 AN: 147304 Hom.: 2647 Cov.: 0

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0381

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.188 AC: 35594 AN: 189446 Hom.: 1534 AF XY: 0.191 AC XY: 19633 AN XY: 102570

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.0449

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.189 AC: 266437 AN: 1410118 Hom.: 8381 AF XY: 0.189 AC XY: 132363 AN XY: 699364

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0947

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0227

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.189 AC: 27905 AN: 147396 Hom.: 2644 Cov.: 0 AF XY: 0.186 AC XY: 13339 AN XY: 71558

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;