rs1498095

Positions:

• chr3-42051930-T-C

Variant summary

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

The ENST00000673621.2(TRAK1):​c.-122-35174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,240 control chromosomes in the GnomAD database, including 623 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 0.086 (623 hom., cov: 32)
• Consequence: TRAK1 ENST00000673621.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAK1	XM_017005909.2	c.-518-35174T>C		intron_variant
TRAK1	XM_017005911.2	c.-518-35174T>C		intron_variant
TRAK1	XM_047447718.1	c.-518-35174T>C		intron_variant
TRAK1	XM_047447722.1	c.-518-35174T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAK1	ENST00000487159.5	c.-518-35174T>C		intron_variant		5
TRAK1	ENST00000672026.1	c.-518-35174T>C		intron_variant
TRAK1	ENST00000673621.2	c.-122-35174T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13117 AN: 152122 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0863 AC: 13137 AN: 152240 Hom.: 623 Cov.: 32 AF XY: 0.0860 AC XY: 6404 AN XY: 74430

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0853

Alfa AF: 0.106 Hom.: 766

Bravo AF: 0.0807

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1498095; hg19: chr3-42093422;