NM_005488.3:c.52+104G>C

Variant names:

• chr22-35300084-G-C
• rs138728
• NM_005488.3:c.52+104G>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005488.3(TOM1):​c.52+104G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,334,146 control chromosomes in the GnomAD database, including 259,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (22871 hom., cov: 35)
  • Exomes 𝑓: 0.63 (237103 hom.)
• Consequence: TOM1 NM_005488.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-35300084-G-C is Benign according to our data. Variant chr22-35300084-G-C is described in ClinVar as [Benign]. Clinvar id is 2687946.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	c.52+104G>C		intron_variant	Intron 1 of 14	ENST00000449058.7	NP_005479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOM1	ENST00000449058.7	c.52+104G>C		intron_variant	Intron 1 of 14	1	NM_005488.3	ENSP00000394466.2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78080 AN: 152136 Hom.: 22887 Cov.: 35

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.628 AC: 742556 AN: 1181892 Hom.: 237103 AF XY: 0.628 AC XY: 371085 AN XY: 590930

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.609

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.513 AC: 78061 AN: 152254 Hom.: 22871 Cov.: 35 AF XY: 0.513 AC XY: 38157 AN XY: 74448

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.561

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: 0.579

Alfa AF: 0.448 Hom.: 973

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.77

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: rs138728; hg19: chr22-35696077; COSMIC: COSV53334059; COSMIC: COSV53334059;