Genetic Variant NM_005488.3:c.52+104G>A (chr22-35300084-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005488.3(TOM1):c.52+104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 1,336,382 control chromosomes in the GnomAD database, including 2,552 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 0.081 ( 775 hom., cov: 35)

Exomes 𝑓: 0.047 ( 1777 hom. )

Consequence

TOM1
NM_005488.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1	NM_005488.3 link	c.52+104G>A		intron_variant	Intron 1 of 14	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.52+104G>A		intron_variant	Intron 1 of 14	1	NM_005488.3	ENSP00000394466.2		O60784-1

Frequencies

GnomAD3 genomes

AF:

0.0804

AC:

12226

AN:

152156

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.0782

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0569

GnomAD4 exome

AF:

0.0475

AC:

56211

AN:

1184108

Hom.:

1777

AF XY:

0.0464

AC XY:

27463

AN XY:

592090

show subpopulations

Gnomad4 AFR exome

AF:

0.187

Gnomad4 AMR exome

AF:

0.0222

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0772

Gnomad4 SAS exome

AF:

0.0304

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0457

Gnomad4 OTH exome

AF:

0.0539

GnomAD4 genome

AF:

0.0806

AC:

12270

AN:

152274

Hom.:

775

Cov.:

AF XY:

0.0773

AC XY:

5759

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.0339

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.0782

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.0353

Gnomad4 NFE

AF:

0.0458

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0404

Hom.:

973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.3

DANN

Benign

0.96

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over