Genetic Variant TOM1:c.-120G>A (chr22-35299809-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000411850.5(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 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 was made for transcript

Our verdict: Benign. The variant received -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 link	c.-120G>A		upstream_gene_variant		ENST00000449058.7	NP_005479.1	O60784-1B3KUF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7 link	c.-120G>A		upstream_gene_variant		1	NM_005488.3	ENSP00000394466.2		O60784-1

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

African (AFR)

AF:

0.168

AC:

3851

AN:

22916

American (AMR)

AF:

0.566

AC:

17711

AN:

31288

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

13860

AN:

20128

East Asian (EAS)

AF:

0.520

AC:

17197

AN:

33066

South Asian (SAS)

AF:

0.578

AC:

38338

AN:

66384

European-Finnish (FIN)

AF:

0.610

AC:

25028

AN:

41060

Middle Eastern (MID)

AF:

0.601

AC:

2054

AN:

3418

European-Non Finnish (NFE)

AF:

0.651

AC:

480688

AN:

738054

Other (OTH)

AF:

0.612

AC:

27080

AN:

44260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

10984

21968

32953

43937

54921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.507

AC:

77222

AN:

152184

Hom.:

22668

Cov.:

AF XY:

0.507

AC XY:

37724

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.191

AC:

7948

AN:

41542

American (AMR)

AF:

0.557

AC:

8524

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

2388

AN:

3468

East Asian (EAS)

AF:

0.534

AC:

2765

AN:

5176

South Asian (SAS)

AF:

0.578

AC:

2789

AN:

4822

European-Finnish (FIN)

AF:

0.618

AC:

6537

AN:

10584

Middle Eastern (MID)

AF:

0.589

AC:

172

AN:

292

European-Non Finnish (NFE)

AF:

0.651

AC:

44271

AN:

67978

Other (OTH)

AF:

0.576

AC:

1219

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1743

3486

5229

6972

8715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.552

Hom.:

3329

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

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

(source)

DANN

Benign

0.81

PhyloP100

-0.95

PromoterAI

0.091

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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22-35299809-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over