rs2267331

Positions:

• chr22-35326133-T-C

Variant summary

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

The NM_005488.3(TOM1):​c.649-1138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 152,326 control chromosomes in the GnomAD database, including 237 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 0.035 (237 hom., cov: 33)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1	NM_005488.3	c.649-1138T>C		intron_variant		ENST00000449058.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1	ENST00000449058.7	c.649-1138T>C		intron_variant		1	NM_005488.3	P3

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5274 AN: 152208 Hom.: 227 Cov.: 33

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0348 AC: 5303 AN: 152326 Hom.: 237 Cov.: 33 AF XY: 0.0374 AC XY: 2787 AN XY: 74490

Gnomad4 AFR AF: 0.00818

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0477

Alfa AF: 0.0335 Hom.: 78

Bravo AF: 0.0445

Asia WGS AF: 0.105 AC: 364 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	4.3
DANN	Benign	0.68

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: rs2267331; hg19: chr22-35722126;