Variant 3-42125451-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001349245.1(TRAK1):c.-190C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,614,130 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 99 hom. )

Consequence

TRAK1
NM_001349245.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.701

Variant links:

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 links:

TRAK1 (HGNC:):

TRAK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 3-42125451-C-T is Benign according to our data. Variant chr3-42125451-C-T is described in ClinVar as [Benign]. Clinvar id is 1600230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-42125451-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00275 (419/152276) while in subpopulation SAS AF= 0.0383 (185/4824). AF 95% confidence interval is 0.0338. There are 5 homozygotes in gnomad4. There are 229 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAK1	NM_001042646.3 linkuse as main transcript	c.123C>T	p.Val41Val	synonymous_variant	2/16	ENST00000327628.10	NP_001036111.1	Q9UPV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAK1	ENST00000327628.10 linkuse as main transcript	c.123C>T	p.Val41Val	synonymous_variant	2/16	1	NM_001042646.3	ENSP00000328998.5		Q9UPV9-1

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

419

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00173

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00624

AC:

1557

AN:

249354

Hom.:

AF XY:

0.00799

AC XY:

1081

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00646

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.0379

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00810

GnomAD4 exome

AF:

0.00375

AC:

5488

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3578

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00528

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0388

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.00275

AC:

419

AN:

152276

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0383

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00174

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00213

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 06, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.8

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over