Variant 3-42091491-G-A 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_001042646.3(TRAK1):c.22G>A(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,348 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 11 hom. )

Consequence

TRAK1
NM_001042646.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.179

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:

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 (MetaRNN=0.0030530095).

BP6

Variant 3-42091491-G-A is Benign according to our data. Variant chr3-42091491-G-A is described in ClinVar as [Benign]. Clinvar id is 712455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00719 (1094/152206) while in subpopulation AFR AF= 0.0241 (1001/41516). AF 95% confidence interval is 0.0229. There are 10 homozygotes in gnomad4. There are 512 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAK1	NM_001042646.3 linkuse as main transcript	c.22G>A	p.Gly8Arg	missense_variant	1/16	ENST00000327628.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAK1	ENST00000327628.10 linkuse as main transcript	c.22G>A	p.Gly8Arg	missense_variant	1/16	1	NM_001042646.3	P1	Q9UPV9-1

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1088

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00177

AC:

439

AN:

248428

Hom.:

AF XY:

0.00126

AC XY:

170

AN XY:

134850

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.000968

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000708

AC:

1034

AN:

1461142

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00719

AC:

1094

AN:

152206

Hom.:

Cov.:

AF XY:

0.00688

AC XY:

512

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.00854

ESP6500AA

AF:

0.0275

AC:

106

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.00218

AC:

264

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.089

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.67

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.30

REVEL

Benign

0.059

Sift

Benign

0.47

Sift4G

Benign

0.71

Polyphen

0.010

Vest4

0.12

MutPred

0.21

Gain of helix (P = 0.0199);

MVP

0.32

MPC

0.30

ClinPred

0.0070

GERP RS

-2.2

Varity_R

0.036

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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