NM_001042646.3:c.84C>T

Variant names:

• chr3-42091553-C-T
• rs148528673
• NM_001042646.3:c.84C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001042646.3(TRAK1):​c.84C>T​(p.Asn28Asn) 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:3
• Conservation: PhyloP100: 0.493
• Publications: 1 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 -17 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 Benign/Likely_benign. ClinVar VariationId 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.
• BS2: High AC in GnomAd4 at 119 AD gene.

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.84C>T	p.Asn28Asn	synonymous	Exon 1 of 16	NP_001036111.1	Q9UPV9-1
	TRAK1	NM_001349246.2		c.84C>T	p.Asn28Asn	synonymous	Exon 1 of 16	NP_001336175.1
	TRAK1	NM_001265608.2		c.84C>T	p.Asn28Asn	synonymous	Exon 1 of 14	NP_001252537.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK1	ENST00000327628.10	TSL:1 MANE Select	c.84C>T	p.Asn28Asn	synonymous	Exon 1 of 16	ENSP00000328998.5	Q9UPV9-1
	TRAK1	ENST00000673621.3		c.175+4153C>T		intron	N/A	ENSP00000500819.2	A0A5F9ZI06
	TRAK1	ENST00000487159.5	TSL:5	c.-222+4153C>T		intron	N/A	ENSP00000486713.1	A0A0D9SFL5

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

GnomAD2 exomes AF: 0.000199 AC: 49 AN: 246370 AF XY: 0.000164

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 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

African (AFR) AF: 0.00292 AC: 97 AN: 33256

American (AMR) AF: 0.000205 AC: 9 AN: 43850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5758

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1111426

Other (OTH) AF: 0.000514 AC: 31 AN: 60288

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

African (AFR) AF: 0.00243 AC: 101 AN: 41582

American (AMR) AF: 0.000392 AC: 6 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000392 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.7
DANN	Benign	0.84
PhyloP100		0.49
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	polymorphism

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: rs148528673; hg19: chr3-42133045;