ENST00000411850.5:c.-120G>C

Variant names:

• chr22-35299809-G-C
• rs4461
• ENST00000411850.5:c.-120G>C

Variant summary

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

The ENST00000411850.5(TOM1):​c.-120G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,002,712 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: 34)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: TOM1 ENST00000411850.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 0 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=-0.68).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000411850.5. 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_001135729.2		c.-48+431G>C		intron	N/A	NP_001129201.1	O60784-4
	TOM1	NM_005488.3	MANE Select	c.-120G>C		upstream_gene	N/A	NP_005479.1	O60784-1
	TOM1	NM_001135732.2		c.-120G>C		upstream_gene	N/A	NP_001129204.1	O60784-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1	ENST00000411850.5	TSL:1	c.-120G>C		5_prime_UTR	Exon 1 of 15	ENSP00000413697.1	O60784-2
	TOM1	ENST00000425375.5	TSL:2	c.-120G>C		5_prime_UTR	Exon 1 of 14	ENSP00000394924.1	O60784-3
	TOM1	ENST00000456128.5	TSL:5	c.-120G>C		5_prime_UTR	Exon 1 of 10	ENSP00000393714.1	B0QY01

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000199 AC: 2 AN: 1002712 Hom.: 0 Cov.: 13 AF XY: 0.00000395 AC XY: 2 AN XY: 506074

African (AFR) AF: 0.00 AC: 0 AN: 22946

American (AMR) AF: 0.00 AC: 0 AN: 31332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20154

East Asian (EAS) AF: 0.00 AC: 0 AN: 33100

South Asian (SAS) AF: 0.00 AC: 0 AN: 66448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3420

European-Non Finnish (NFE) AF: 0.00000270 AC: 2 AN: 739826

Other (OTH) AF: 0.00 AC: 0 AN: 44362

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.95
PromoterAI		0.14	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: rs4461; hg19: chr22-35695802;