chr17-17843975-A-G

Position:

• chr17-17843975-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.*3660T>C 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 152,136 control chromosomes in the GnomAD database, including 25,377 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 (25357 hom., cov: 32)
  • Exomes 𝑓: 0.54 (20 hom.)
• Consequence: TOM1L2 NM_001082968.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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=-0.91).
• 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	Protein	UniProt
TOM1L2	NM_001082968.2	c.*3660T>C		3_prime_UTR_variant	15/15	ENST00000379504.8	NP_001076437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOM1L2	ENST00000379504.8	c.*3660T>C		3_prime_UTR_variant	15/15	2	NM_001082968.2	ENSP00000368818.3
TOM1L2	ENST00000581396.5	c.*3660T>C		3_prime_UTR_variant	14/14	1		ENSP00000464297.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85919 AN: 151898 Hom.: 25341 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.542 AC: 65 AN: 120 Hom.: 20 Cov.: 0 AF XY: 0.537 AC XY: 44 AN XY: 82

Gnomad4 EAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.566 AC: 85987 AN: 152016 Hom.: 25357 Cov.: 32 AF XY: 0.553 AC XY: 41059 AN XY: 74286

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.0793

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.560

Alfa AF: 0.596 Hom.: 19693

Bravo AF: 0.561

Asia WGS AF: 0.260 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3183702; hg19: chr17-17747289;