3-42091553-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001042646.3(TRAK1):c.84C>T(p.Asn28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,612,004 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (3 hom.)
• Consequence: TRAK1 NM_001042646.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.493

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-42091553-C-T is Benign according to our data. Variant chr3-42091553-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1298912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.493 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAK1	NM_001042646.3	c.84C>T	p.Asn28=	synonymous_variant	1/16	ENST00000327628.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAK1	ENST00000327628.10	c.84C>T	p.Asn28=	synonymous_variant	1/16	1	NM_001042646.3	P1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000199 AC: 49 AN: 246370 Hom.: 0 AF XY: 0.000164 AC XY: 22 AN XY: 133954

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.000180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.000670

GnomAD4 exome AF: 0.000156 AC: 227 AN: 1459706 Hom.: 3 Cov.: 30 AF XY: 0.000150 AC XY: 109 AN XY: 726304

Gnomad4 AFR exome AF: 0.00292

Gnomad4 AMR exome AF: 0.000205

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000630

Gnomad4 OTH exome AF: 0.000514

GnomAD4 genome AF: 0.000781 AC: 119 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000752 AC XY: 56 AN XY: 74476

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000392 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 13, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	7.7
Dann	Benign	0.84

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: rs148528673; hg19: chr3-42133045;