rs2236513

chr17-17844052-A-Cchr17-17844052-A-G

Variant summary

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

The NM_001082968.2(TOM1L2):c.*3583T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,338 control chromosomes in the GnomAD database, including 25,424 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 0.57 (25382 hom., cov: 33)
  • Exomes 𝑓: 0.55 (42 hom.)
• Consequence: TOM1L2 NM_001082968.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

Genes affected

TOM1L2 (HGNC:11984): (target of myb1 like 2 membrane trafficking protein) This gene belongs to a small gene family whose members have an N-terminal VHS domain followed by a GAT domain; domains which typically participate in vesicular trafficking. The canonical protein encoded by this gene also has a C-terminal clathrin binding motif. This protein has been shown to interact with Tollip, clathrin and ubiquitin and is thought to play a role in endosomal sorting. This gene resides in the 3.7 Mb deletion of chromosome region 17p11.2 that is associated with Smith-Magenis syndrome. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1L2	NM_001082968.2	c.*3583T>G		3_prime_UTR_variant	15/15	ENST00000379504.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1L2	ENST00000379504.8	c.*3583T>G		3_prime_UTR_variant	15/15	2	NM_001082968.2	P1
TOM1L2	ENST00000581396.5	c.*3583T>G		3_prime_UTR_variant	14/14	1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85978 AN: 151944 Hom.: 25366 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.547 AC: 151 AN: 276 Hom.: 42 Cov.: 0 AF XY: 0.589 AC XY: 126 AN XY: 214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.566 AC: 86046 AN: 152062 Hom.: 25382 Cov.: 33 AF XY: 0.553 AC XY: 41100 AN XY: 74336

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.0792

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.561

Alfa AF: 0.566 Hom.: 4015

Bravo AF: 0.561

Asia WGS AF: 0.259 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.60
Dann	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2236513; hg19: chr17-17747366;