Genetic Variant TOM1L1:p.Ile170Met (chr17-54914650-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005486.3(TOM1L1):c.510C>G(p.Ile170Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

TOM1L1
NM_005486.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.574

Publications

2 publications found

Variant links:

Genes affected

TOM1L1 (HGNC:11983): (target of myb1 like 1 membrane trafficking protein) Enables clathrin binding activity and protein kinase binding activity. Involved in negative regulation of mitotic nuclear division; positive regulation of protein phosphorylation; and signal transduction. Located in cytosol and endosome. [provided by Alliance of Genome Resources, Apr 2022]

TOM1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011748046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005486.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOM1L1	NM_005486.3	MANE Select	c.510C>G	p.Ile170Met	missense	Exon 6 of 16	NP_005477.2	O75674-1
TOM1L1	NM_001321174.2		c.279C>G	p.Ile93Met	missense	Exon 4 of 14	NP_001308103.1	O75674-3
TOM1L1	NM_001321175.2		c.279C>G	p.Ile93Met	missense	Exon 7 of 17	NP_001308104.1	O75674-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOM1L1	ENST00000575882.6	TSL:1 MANE Select	c.510C>G	p.Ile170Met	missense	Exon 6 of 16	ENSP00000460823.1	O75674-1
TOM1L1	ENST00000575333.5	TSL:1	c.510C>G	p.Ile170Met	missense	Exon 6 of 10	ENSP00000458918.1	O75674-2
TOM1L1	ENST00000576932.5	TSL:1	n.279C>G		non_coding_transcript_exon	Exon 4 of 11	ENSP00000461876.1	I3NI44

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000123

AC:

AN:

251292

AF XY:

0.0000957

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461014

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.000832

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111364

Other (OTH)

AF:

0.0000166

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000394

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00115

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.045

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.69

M_CAP

Benign

0.0043

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.57

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.29

REVEL

Benign

0.046

Sift

Benign

0.24

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.091

MutPred

0.20

Gain of loop (P = 0.0502)

MVP

0.38

MPC

0.15

ClinPred

0.020

GERP RS

2.7

Varity_R

0.025

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over