Variant chr17-54930092-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005486.3(TOM1L1):c.740G>A(p.Arg247Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TOM1L1
NM_005486.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3812557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1L1	NM_005486.3 linkuse as main transcript	c.740G>A	p.Arg247Gln	missense_variant	8/16	ENST00000575882.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1L1	ENST00000575882.6 linkuse as main transcript	c.740G>A	p.Arg247Gln	missense_variant	8/16	1	NM_005486.3	P1	O75674-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251218

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000555

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.740G>A (p.R247Q) alteration is located in exon 8 (coding exon 8) of the TOM1L1 gene. This alteration results from a G to A substitution at nucleotide position 740, causing the arginine (R) at amino acid position 247 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

.;T;.;.;T;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

.;D;D;.;D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.38

T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.9

L;L;.;.;.;.;L

MutationTaster

Benign

0.99

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.5

.;.;D;D;.;D;.

REVEL

Benign

0.28

Sift

Benign

0.034

.;.;D;D;.;D;.

Sift4G

Benign

0.062

T;T;T;D;T;D;T

Polyphen

1.0

.;D;.;.;.;.;.

Vest4

0.38

MVP

0.80

MPC

0.54

ClinPred

0.90

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over