dbSNP rs2236513: TOM1L2:c.*3583T>G (chr17-17844052-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.607

Publications

23 publications found

Variant links:

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]

TOM1L2 links:

ENSG00000301763 (HGNC:):

ENSG00000301763 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TOM1L2	NM_001082968.2 link	c.*3583T>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000379504.8	NP_001076437.1	Q6ZVM7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOM1L2	ENST00000379504.8 link	c.*3583T>G	3_prime_UTR_variant	Exon 15 of 15	2	NM_001082968.2	ENSP00000368818.3	Q6ZVM7-1
TOM1L2	ENST00000581396.6 link	c.*3583T>G	3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000464297.1	Q6ZVM7-2
ENSG00000301763	ENST00000781607.1 link	n.67+1443A>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85978

AN:

151944

Hom.:

25366

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.589

AC XY:

126

AN XY:

214

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.357

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.558

AC:

125

AN:

224

Other (OTH)

AF:

0.682

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.566

AC:

86046

AN:

152062

Hom.:

25382

Cov.:

AF XY:

0.553

AC XY:

41100

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.583

AC:

24178

AN:

41458

American (AMR)

AF:

0.475

AC:

7253

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2015

AN:

3470

East Asian (EAS)

AF:

0.0792

AC:

410

AN:

5180

South Asian (SAS)

AF:

0.284

AC:

1368

AN:

4818

European-Finnish (FIN)

AF:

0.563

AC:

5962

AN:

10598

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.633

AC:

43003

AN:

67948

Other (OTH)

AF:

0.561

AC:

1184

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1871

3741

5612

7482

9353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.565

Hom.:

4747

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

(source)

DANN

Benign

0.30

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over