rs2267332

Variant names:

• chr22-35328271-G-C
• rs2267332
• NM_005488.3:c.765+884G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005488.3(TOM1):​c.765+884G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,254 control chromosomes in the GnomAD database, including 461 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 0.067 (461 hom., cov: 33)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 6 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: AD, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 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.765+884G>C		intron	N/A	NP_005479.1	O60784-1
	TOM1	NM_001135732.2		c.765+884G>C		intron	N/A	NP_001129204.1	O60784-2
	TOM1	NM_001135729.2		c.666+884G>C		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.765+884G>C		intron	N/A	ENSP00000394466.2	O60784-1
	TOM1	ENST00000411850.5	TSL:1	c.765+884G>C		intron	N/A	ENSP00000413697.1	O60784-2
	TOM1	ENST00000953252.1		c.765+884G>C		intron	N/A	ENSP00000623311.1

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10260 AN: 152136 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0851

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0675

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0673 AC: 10250 AN: 152254 Hom.: 461 Cov.: 33 AF XY: 0.0681 AC XY: 5068 AN XY: 74438

African (AFR) AF: 0.0176 AC: 732 AN: 41568

American (AMR) AF: 0.0571 AC: 874 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0851 AC: 295 AN: 3468

East Asian (EAS) AF: 0.115 AC: 596 AN: 5162

South Asian (SAS) AF: 0.0669 AC: 323 AN: 4828

European-Finnish (FIN) AF: 0.0934 AC: 991 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6163 AN: 68012

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0795 Hom.: 66

Bravo AF: 0.0621

Asia WGS AF: 0.0850 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.73
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: rs2267332; hg19: chr22-35724264;