rs10483190

Variant names:

• chr22-35326018-G-A
• rs10483190
• NM_005488.3:c.649-1253G>A

Variant summary

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

The NM_005488.3(TOM1):​c.649-1253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,146 control chromosomes in the GnomAD database, including 3,256 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 0.18 (3256 hom., cov: 33)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3	c.649-1253G>A		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.649-1253G>A		intron_variant	Intron 6 of 14	1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27385 AN: 152026 Hom.: 3243 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.180 AC: 27447 AN: 152146 Hom.: 3256 Cov.: 33 AF XY: 0.179 AC XY: 13329 AN XY: 74412

African (AFR) AF: 0.328 AC: 13618 AN: 41460

American (AMR) AF: 0.207 AC: 3160 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3466

East Asian (EAS) AF: 0.181 AC: 937 AN: 5180

South Asian (SAS) AF: 0.0957 AC: 462 AN: 4830

European-Finnish (FIN) AF: 0.0923 AC: 978 AN: 10596

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7436 AN: 68010

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.138 Hom.: 5924

Bravo AF: 0.199

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.20
PhyloP100		-0.39
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: rs10483190; hg19: chr22-35722011;