22-35315105-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005488.3(TOM1):c.53-2772A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,892 control chromosomes in the GnomAD database, including 23,165 homozygotes. 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: 𝑓 0.52 (23165 hom., cov: 30)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1	NM_005488.3	c.53-2772A>G		intron_variant		ENST00000449058.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1	ENST00000449058.7	c.53-2772A>G		intron_variant		1	NM_005488.3	P3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78592 AN: 151774 Hom.: 23180 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.517 AC: 78579 AN: 151892 Hom.: 23165 Cov.: 30 AF XY: 0.516 AC XY: 38306 AN XY: 74220

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.582

Alfa AF: 0.638 Hom.: 46472

Bravo AF: 0.503

Asia WGS AF: 0.541 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.38

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: rs138777; hg19: chr22-35711098;