rs1995137

Positions:

• chr3-42089923-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAK1	NM_001349245.1	c.-222+2523A>G		intron_variant			NP_001336174.1
TRAK1	XM_017005909.2	c.-222+2523A>G		intron_variant			XP_016861398.1
TRAK1	XM_017005911.2	c.-222+2523A>G		intron_variant			XP_016861400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000484786.5	c.-222+2523A>G		intron_variant		5		ENSP00000487488
TRAK1	ENST00000487159.5	c.-222+2523A>G		intron_variant		5		ENSP00000486713
TRAK1	ENST00000672026.1	c.-222+2523A>G		intron_variant				ENSP00000500099
TRAK1	ENST00000673621.2	c.175+2523A>G		intron_variant				ENSP00000500819

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

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.572

Alfa AF: 0.574 Hom.: 45891

Bravo AF: 0.564

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1995137; hg19: chr3-42131415;