3-42137834-G-C

Variant names:

• chr3-42137834-G-C
• rs11709411
• NM_001042646.3:c.286+12220G>C

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+12220G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,976 control chromosomes in the GnomAD database, including 29,465 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 0.62 (29465 hom., cov: 31)
• Consequence: TRAK1 NM_001042646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 3 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):

• developmental and epileptic encephalopathy, 68

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042646.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	NM_001042646.3	MANE Select	c.286+12220G>C		intron	N/A	NP_001036111.1	Q9UPV9-1
	TRAK1	NM_001349246.2		c.286+12220G>C		intron	N/A	NP_001336175.1
	TRAK1	NM_001349245.1		c.-27+12220G>C		intron	N/A	NP_001336174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.286+12220G>C		intron	N/A	ENSP00000328998.5	Q9UPV9-1
	TRAK1	ENST00000673621.3		c.370+12220G>C		intron	N/A	ENSP00000500819.2	A0A5F9ZI06
	TRAK1	ENST00000487159.5	TSL:5	c.-27+12220G>C		intron	N/A	ENSP00000486713.1	A0A0D9SFL5

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94099 AN: 151858 Hom.: 29428 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.620 AC: 94183 AN: 151976 Hom.: 29465 Cov.: 31 AF XY: 0.623 AC XY: 46271 AN XY: 74294

African (AFR) AF: 0.669 AC: 27743 AN: 41440

American (AMR) AF: 0.651 AC: 9942 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2440 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2857 AN: 5154

South Asian (SAS) AF: 0.771 AC: 3711 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6088 AN: 10548

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39431 AN: 67956

Other (OTH) AF: 0.633 AC: 1335 AN: 2110

Alfa AF: 0.443 Hom.: 1109

Bravo AF: 0.626

Asia WGS AF: 0.691 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.14
PhyloP100		-0.67
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: rs11709411; hg19: chr3-42179326;