22-35299809-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000411850(TOM1):​c.-120G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,152,758 control chromosomes in the GnomAD database, including 223,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (22668 hom., cov: 34)
  • Exomes 𝑓: 0.63 (200692 hom.)
• Consequence: TOM1 ENST00000411850 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.955

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 22-35299809-G-A is Benign according to our data. Variant chr22-35299809-G-A is described in ClinVar as [Benign]. Clinvar id is 2688109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3	c.-120G>A		upstream_gene_variant		ENST00000449058.7	NP_005479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7	c.-120G>A		upstream_gene_variant		1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77241 AN: 152066 Hom.: 22684 Cov.: 34

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.625 AC: 625807 AN: 1000574 Hom.: 200692 Cov.: 13 AF XY: 0.625 AC XY: 315813 AN XY: 505020

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.578

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.507 AC: 77222 AN: 152184 Hom.: 22668 Cov.: 34 AF XY: 0.507 AC XY: 37724 AN XY: 74408

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.576

Alfa AF: 0.567 Hom.: 3316

Bravo AF: 0.492

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.5
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs4461; hg19: chr22-35695802; COSMIC: COSV53333205; COSMIC: COSV53333205;