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GeneBe

3-42125451-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001042646.3(TRAK1):c.123C>T(p.Val41=) variant causes a synonymous 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_001042646.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars. Variant chr3-42125451-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.701 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRAK1NM_001042646.3 linkuse as main transcriptc.123C>T p.Val41= synonymous_variant 2/16 ENST00000327628.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRAK1ENST00000327628.10 linkuse as main transcriptc.123C>T p.Val41= synonymous_variant 2/161 NM_001042646.3 P1Q9UPV9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00275
AC:
419
AN:
152156
Hom.:
5
Cov.:
32
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.:
35
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.:
99
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00275
AC:
419
AN:
152276
Hom.:
5
Cov.:
32
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.:
0
Bravo
AF:
0.00213
Asia WGS
AF:
0.0160
AC:
57
AN:
3478
EpiCase
AF:
0.00278
EpiControl
AF:
0.00296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 06, 2024- -

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.

Other links and lift over

dbSNP: rs61742102; hg19: chr3-42166943; API