rs9311300

Positions:

• chr3-42144070-G-A

Variant summary

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

The NM_001042646.3(TRAK1):​c.286+18456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,986 control chromosomes in the GnomAD database, including 37,763 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 0.70 (37763 hom., cov: 31)
• Consequence: TRAK1 NM_001042646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAK1	NM_001042646.3	c.286+18456G>A		intron_variant		ENST00000327628.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAK1	ENST00000327628.10	c.286+18456G>A		intron_variant		1	NM_001042646.3	P1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106408 AN: 151868 Hom.: 37718 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.701 AC: 106512 AN: 151986 Hom.: 37763 Cov.: 31 AF XY: 0.701 AC XY: 52110 AN XY: 74292

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.696

Alfa AF: 0.698 Hom.: 22175

Bravo AF: 0.701

Asia WGS AF: 0.748 AC: 2598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.43

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: rs9311300; hg19: chr3-42185562;