rs6481

Variant names:

• chr22-35305905-A-AGAGTG
• rs6481
• NM_005488.3:c.52+5927_52+5928insGTGGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005488.3(TOM1):​c.52+5927_52+5928insGTGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22655 hom., cov: 0)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 7 publications found

Genes affected

TOM1 (HGNC:11982): (target of myb1 membrane trafficking protein) This gene was identified as a target of the v-myb oncogene. The encoded protein shares its N-terminal domain in common with proteins associated with vesicular trafficking at the endosome. It is recruited to the endosomes by its interaction with endofin. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

TOM1 Gene-Disease associations (from GenCC):

• immune system disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• immunodeficiency 85 and autoimmunity

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005488.3. 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
	TOM1	NM_005488.3	MANE Select	c.52+5927_52+5928insGTGGA		intron	N/A	NP_005479.1	O60784-1
	TOM1	NM_001135732.2		c.52+5927_52+5928insGTGGA		intron	N/A	NP_001129204.1	O60784-2
	TOM1	NM_001135729.2		c.-48+6529_-48+6530insGTGGA		intron	N/A	NP_001129201.1	O60784-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1	ENST00000449058.7	TSL:1 MANE Select	c.52+5925_52+5926insGAGTG		intron	N/A	ENSP00000394466.2	O60784-1
	TOM1	ENST00000411850.5	TSL:1	c.52+5925_52+5926insGAGTG		intron	N/A	ENSP00000413697.1	O60784-2
	TOM1	ENST00000953252.1		c.52+5925_52+5926insGAGTG		intron	N/A	ENSP00000623311.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77654 AN: 151408 Hom.: 22671 Cov.: 0

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.593

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.512 AC: 77634 AN: 151526 Hom.: 22655 Cov.: 0 AF XY: 0.512 AC XY: 37887 AN XY: 74026

African (AFR) AF: 0.211 AC: 8723 AN: 41424

American (AMR) AF: 0.560 AC: 8520 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2380 AN: 3460

East Asian (EAS) AF: 0.532 AC: 2720 AN: 5116

South Asian (SAS) AF: 0.580 AC: 2790 AN: 4814

European-Finnish (FIN) AF: 0.614 AC: 6438 AN: 10488

Middle Eastern (MID) AF: 0.586 AC: 170 AN: 290

European-Non Finnish (NFE) AF: 0.651 AC: 44077 AN: 67710

Other (OTH) AF: 0.578 AC: 1216 AN: 2104

Alfa AF: 0.567 Hom.: 3200

Bravo AF: 0.497

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6481;

hg19: chr22-35701898;