NM_001042646.3:c.52_62dupGGACTCTGCCA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_001042646.3(TRAK1):​c.52_62dupGGACTCTGCCA​(p.His21GlnfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TRAK1
NM_001042646.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.476
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.978 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-42091512-C-CCTCTGCCAGGA is Pathogenic according to our data. Variant chr3-42091512-C-CCTCTGCCAGGA is described in ClinVar as [Pathogenic]. Clinvar id is 3721550.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRAK1NM_001042646.3 linkc.52_62dupGGACTCTGCCA p.His21GlnfsTer40 frameshift_variant Exon 1 of 16 ENST00000327628.10 NP_001036111.1 Q9UPV9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRAK1ENST00000327628.10 linkc.52_62dupGGACTCTGCCA p.His21GlnfsTer40 frameshift_variant Exon 1 of 16 1 NM_001042646.3 ENSP00000328998.5 Q9UPV9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Pathogenic:1
Dec 02, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.His21Glnfs*40) in the TRAK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRAK1 are known to be pathogenic (PMID: 28364549, 28940097). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TRAK1-related conditions. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42133004; API