3-42142869-C-T

Position:

• chr3-42142869-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042646.3(TRAK1):​c.286+17255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,280 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.072 (495 hom., cov: 33)
• Consequence: TRAK1 NM_001042646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.286+17255C>T		intron_variant		ENST00000327628.10	NP_001036111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000327628.10	c.286+17255C>T		intron_variant		1	NM_001042646.3	ENSP00000328998.5

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11014 AN: 152162 Hom.: 495 Cov.: 33

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.0789

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0723 AC: 11014 AN: 152280 Hom.: 495 Cov.: 33 AF XY: 0.0714 AC XY: 5316 AN XY: 74444

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0850

Gnomad4 NFE AF: 0.0995

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0822 Hom.: 374

Bravo AF: 0.0657

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.080
DANN	Benign	0.65

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: rs9852952; hg19: chr3-42184361;