Variant 22-35299809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.955

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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_001135729.2 link	c.-48+431G>A		intron_variant	Intron 1 of 14		NP_001129201.1	O60784-4B3KUF5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TOM1	ENST00000411850 link	c.-120G>A	5_prime_UTR_variant	Exon 1 of 15	1	ENSP00000413697.1	O60784-2
TOM1	ENST00000425375 link	c.-120G>A	5_prime_UTR_variant	Exon 1 of 14	2	ENSP00000394924.1	O60784-3
TOM1	ENST00000456128 link	c.-120G>A	5_prime_UTR_variant	Exon 1 of 10	5	ENSP00000393714.1	B0QY01

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77241

AN:

152066

Hom.:

22684

Cov.:

show subpopulations

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.:

AF XY:

0.625

AC XY:

315813

AN XY:

505020

show subpopulations

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.:

AF XY:

0.507

AC XY:

37724

AN XY:

74408

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over