chr3-42089923-A-G

Variant names:

• chr3-42089923-A-G
• rs1995137
• ENST00000673621.3:c.175+2523A>G

Variant summary

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

The NM_001349245.1(TRAK1):​c.-222+2523A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,950 control chromosomes in the GnomAD database, including 24,432 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 0.56 (24432 hom., cov: 31)
• Consequence: TRAK1 NM_001349245.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 8 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):

• developmental and epileptic encephalopathy, 68

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349245.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	NM_001349245.1		c.-222+2523A>G		intron	N/A	NP_001336174.1
	TRAK1	NR_146089.1		n.201+2523A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	ENST00000673621.3		c.175+2523A>G		intron	N/A	ENSP00000500819.2	A0A5F9ZI06
	TRAK1	ENST00000487159.5	TSL:5	c.-222+2523A>G		intron	N/A	ENSP00000486713.1	A0A0D9SFL5
	TRAK1	ENST00000672026.1		c.-222+2523A>G		intron	N/A	ENSP00000500099.1	A0A5F9ZH95

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85677 AN: 151830 Hom.: 24406 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.564 AC: 85752 AN: 151950 Hom.: 24432 Cov.: 31 AF XY: 0.567 AC XY: 42089 AN XY: 74250

African (AFR) AF: 0.531 AC: 22019 AN: 41428

American (AMR) AF: 0.616 AC: 9415 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2105 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2198 AN: 5148

South Asian (SAS) AF: 0.678 AC: 3266 AN: 4820

European-Finnish (FIN) AF: 0.583 AC: 6155 AN: 10550

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38815 AN: 67944

Other (OTH) AF: 0.572 AC: 1207 AN: 2110

Alfa AF: 0.572 Hom.: 64534

Bravo AF: 0.564

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0090
DANN	Benign	0.25
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs1995137; hg19: chr3-42131415;