rs138794

Variant names:

• chr22-35337661-G-A
• rs138794
• NM_005488.3:c.1149-1052G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-35337661-G-A
• chr22-35337661-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005488.3(TOM1):​c.1149-1052G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,182 control chromosomes in the GnomAD database, including 19,767 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 0.48 (19767 hom., cov: 33)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 8 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: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3	c.1149-1052G>A		intron_variant	Intron 11 of 14	ENST00000449058.7	NP_005479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7	c.1149-1052G>A		intron_variant	Intron 11 of 14	1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72368 AN: 152064 Hom.: 19781 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.475 AC: 72352 AN: 152182 Hom.: 19767 Cov.: 33 AF XY: 0.477 AC XY: 35461 AN XY: 74394

African (AFR) AF: 0.190 AC: 7894 AN: 41542

American (AMR) AF: 0.496 AC: 7593 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2128 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2077 AN: 5170

South Asian (SAS) AF: 0.633 AC: 3056 AN: 4828

European-Finnish (FIN) AF: 0.577 AC: 6105 AN: 10580

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.615 AC: 41779 AN: 67974

Other (OTH) AF: 0.488 AC: 1033 AN: 2116

Alfa AF: 0.566 Hom.: 101281

Bravo AF: 0.454

Asia WGS AF: 0.531 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs138794; hg19: chr22-35733654;