rs3183702

Variant names:

• chr17-17843975-A-G
• rs3183702
• NM_001082968.2:c.*3660T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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]

ENSG00000301763 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082968.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1L2	NM_001082968.2	MANE Select	c.*3660T>C		3_prime_UTR	Exon 15 of 15	NP_001076437.1
	TOM1L2	NM_001350332.2		c.*3660T>C		3_prime_UTR	Exon 16 of 16	NP_001337261.1
	TOM1L2	NM_001350333.2		c.*3660T>C		3_prime_UTR	Exon 14 of 14	NP_001337262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1L2	ENST00000379504.8	TSL:2 MANE Select	c.*3660T>C		3_prime_UTR	Exon 15 of 15	ENSP00000368818.3
	TOM1L2	ENST00000581396.6	TSL:1	c.*3660T>C		3_prime_UTR	Exon 14 of 14	ENSP00000464297.1
	ENSG00000301763	ENST00000781607.1		n.67+1366A>G		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.125 AC: 1 AN: 8

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 10 AN: 20

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.541 AC: 40 AN: 74

Other (OTH) AF: 0.875 AC: 14 AN: 16

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

African (AFR) AF: 0.583 AC: 24177 AN: 41480

American (AMR) AF: 0.475 AC: 7251 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3470

East Asian (EAS) AF: 0.0793 AC: 410 AN: 5170

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4820

European-Finnish (FIN) AF: 0.562 AC: 5928 AN: 10554

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 42996 AN: 67936

Other (OTH) AF: 0.560 AC: 1180 AN: 2106

Alfa AF: 0.600 Hom.: 24408

Bravo AF: 0.561

Asia WGS AF: 0.260 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3183702; hg19: chr17-17747289;