22-35300084-G-T

Variant names:

• chr22-35300084-G-T
• rs138728
• NM_005488.3:c.52+104G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005488.3(TOM1):​c.52+104G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,184,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 35)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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+104G>T		intron	N/A	NP_005479.1	O60784-1
	TOM1	NM_001135732.2		c.52+104G>T		intron	N/A	NP_001129204.1	O60784-2
	TOM1	NM_001135729.2		c.-48+706G>T		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+104G>T		intron	N/A	ENSP00000394466.2	O60784-1
	TOM1	ENST00000411850.5	TSL:1	c.52+104G>T		intron	N/A	ENSP00000413697.1	O60784-2
	TOM1	ENST00000953252.1		c.52+104G>T		intron	N/A	ENSP00000623311.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1184614 Hom.: 0 AF XY: 0.00000169 AC XY: 1 AN XY: 592294

African (AFR) AF: 0.00 AC: 0 AN: 26850

American (AMR) AF: 0.00 AC: 0 AN: 32414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22724

East Asian (EAS) AF: 0.00 AC: 0 AN: 34464

South Asian (SAS) AF: 0.00 AC: 0 AN: 73990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4358

European-Non Finnish (NFE) AF: 0.00000222 AC: 2 AN: 900644

Other (OTH) AF: 0.00 AC: 0 AN: 50784

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.8
DANN	Benign	0.72
PhyloP100		-1.1
PromoterAI		-0.055	Neutral

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: rs138728; hg19: chr22-35696077;