22-35315105-A-G

Variant names:

• chr22-35315105-A-G
• rs138777
• NM_005488.3:c.53-2772A>G

Variant summary

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

The NM_005488.3(TOM1):​c.53-2772A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,892 control chromosomes in the GnomAD database, including 23,165 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 0.52 (23165 hom., cov: 30)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 55 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1	NM_005488.3	MANE Select	c.53-2772A>G		intron	N/A	NP_005479.1
	TOM1	NM_001135732.2		c.53-2772A>G		intron	N/A	NP_001129204.1
	TOM1	NM_001135729.2		c.-47-2772A>G		intron	N/A	NP_001129201.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1	ENST00000449058.7	TSL:1 MANE Select	c.53-2772A>G		intron	N/A	ENSP00000394466.2
	TOM1	ENST00000411850.5	TSL:1	c.53-2772A>G		intron	N/A	ENSP00000413697.1
	TOM1	ENST00000447733.5	TSL:2	c.-47-2772A>G		intron	N/A	ENSP00000398876.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78592 AN: 151774 Hom.: 23180 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.517 AC: 78579 AN: 151892 Hom.: 23165 Cov.: 30 AF XY: 0.516 AC XY: 38306 AN XY: 74220

African (AFR) AF: 0.215 AC: 8906 AN: 41430

American (AMR) AF: 0.566 AC: 8640 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2442 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2679 AN: 5156

South Asian (SAS) AF: 0.577 AC: 2776 AN: 4814

European-Finnish (FIN) AF: 0.617 AC: 6486 AN: 10512

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44616 AN: 67930

Other (OTH) AF: 0.582 AC: 1227 AN: 2108

Alfa AF: 0.617 Hom.: 98522

Bravo AF: 0.503

Asia WGS AF: 0.541 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.52
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: rs138777; hg19: chr22-35711098;