rs9872588

Variant names:

• chr3-42142681-T-G
• rs9872588
• NM_001042646.3:c.286+17067T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042646.3(TRAK1):​c.286+17067T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,314 control chromosomes in the GnomAD database, including 516 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 0.074 (516 hom., cov: 33)
• Consequence: TRAK1 NM_001042646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637
• Publications: 2 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):

• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.286+17067T>G		intron_variant	Intron 2 of 15	ENST00000327628.10	NP_001036111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000327628.10	c.286+17067T>G		intron_variant	Intron 2 of 15	1	NM_001042646.3	ENSP00000328998.5

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11293 AN: 152196 Hom.: 516 Cov.: 33

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0741 AC: 11293 AN: 152314 Hom.: 516 Cov.: 33 AF XY: 0.0731 AC XY: 5448 AN XY: 74480

African (AFR) AF: 0.0294 AC: 1221 AN: 41578

American (AMR) AF: 0.0582 AC: 890 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.0563 AC: 292 AN: 5184

South Asian (SAS) AF: 0.0818 AC: 395 AN: 4830

European-Finnish (FIN) AF: 0.0848 AC: 900 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6957 AN: 68018

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0855 Hom.: 1021

Bravo AF: 0.0678

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9872588; hg19: chr3-42184173;