3-42137834-G-C

Position:

• chr3-42137834-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAK1	NM_001042646.3	c.286+12220G>C		intron_variant		ENST00000327628.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAK1	ENST00000327628.10	c.286+12220G>C		intron_variant		1	NM_001042646.3	P1

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

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.633

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.14

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

Other links and lift over

dbSNP: rs11709411; hg19: chr3-42179326;