3-42142869-C-T

Variant names:

• chr3-42142869-C-T
• rs9852952
• NM_001042646.3:c.286+17255C>T

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+17255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,280 control chromosomes in the GnomAD database, including 495 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 0.072 (495 hom., cov: 33)
• Consequence: TRAK1 NM_001042646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAK1	NM_001042646.3	c.286+17255C>T		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+17255C>T		intron_variant	Intron 2 of 15	1	NM_001042646.3	ENSP00000328998.5

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11014 AN: 152162 Hom.: 495 Cov.: 33

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0723 AC: 11014 AN: 152280 Hom.: 495 Cov.: 33 AF XY: 0.0714 AC XY: 5316 AN XY: 74444

African (AFR) AF: 0.0283 AC: 1175 AN: 41568

American (AMR) AF: 0.0563 AC: 862 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.0563 AC: 292 AN: 5184

South Asian (SAS) AF: 0.0795 AC: 384 AN: 4832

European-Finnish (FIN) AF: 0.0850 AC: 901 AN: 10598

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6767 AN: 68010

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0831 Hom.: 418

Bravo AF: 0.0657

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.080
DANN	Benign	0.65
PhyloP100		-1.6
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: rs9852952; hg19: chr3-42184361;