chr3-42144070-G-A

Variant names:

• chr3-42144070-G-A
• rs9311300
• NM_001042646.3:c.286+18456G>A

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+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
• Publications: 3 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=-0.94).
• 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 rank	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.286+18456G>A		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+18456G>A		intron_variant	Intron 2 of 15	1	NM_001042646.3	ENSP00000328998.5

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

African (AFR) AF: 0.630 AC: 26075 AN: 41406

American (AMR) AF: 0.776 AC: 11856 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2442 AN: 3464

East Asian (EAS) AF: 0.972 AC: 5043 AN: 5186

South Asian (SAS) AF: 0.590 AC: 2846 AN: 4822

European-Finnish (FIN) AF: 0.763 AC: 8055 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48158 AN: 67954

Other (OTH) AF: 0.696 AC: 1469 AN: 2112

Alfa AF: 0.706 Hom.: 74297

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
PhyloP100		-3.0
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: rs9311300; hg19: chr3-42185562;