rs2267331

Variant names:

• chr22-35326133-T-C
• rs2267331
• NM_005488.3:c.649-1138T>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.649-1138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 152,326 control chromosomes in the GnomAD database, including 237 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 0.035 (237 hom., cov: 33)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 2 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 Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3	c.649-1138T>C		intron_variant	Intron 6 of 14	ENST00000449058.7	NP_005479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7	c.649-1138T>C		intron_variant	Intron 6 of 14	1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5274 AN: 152208 Hom.: 227 Cov.: 33

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0348 AC: 5303 AN: 152326 Hom.: 237 Cov.: 33 AF XY: 0.0374 AC XY: 2787 AN XY: 74490

African (AFR) AF: 0.00818 AC: 340 AN: 41576

American (AMR) AF: 0.127 AC: 1949 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3464

East Asian (EAS) AF: 0.153 AC: 791 AN: 5178

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4834

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1661 AN: 68030

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0311 Hom.: 98

Bravo AF: 0.0445

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		0.23
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: rs2267331; hg19: chr22-35722126;