Variant 7-4799696-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018059.5(RADIL):c.3056G>A(p.Arg1019His) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,579,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RADIL
NM_018059.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

RADIL (HGNC:22226): (Rap associating with DIL domain) Predicted to enable GTPase binding activity. Acts upstream of or within substrate adhesion-dependent cell spreading. Located in microtubule. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RADIL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RADIL	NM_018059.5 linkuse as main transcript	c.3056G>A	p.Arg1019His	missense_variant	14/15	ENST00000399583.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RADIL	ENST00000399583.4 linkuse as main transcript	c.3056G>A	p.Arg1019His	missense_variant	14/15	5	NM_018059.5	P1	Q96JH8-4
RADIL	ENST00000472999.5 linkuse as main transcript	n.1080G>A		non_coding_transcript_exon_variant	4/5	1
RADIL	ENST00000473130.5 linkuse as main transcript	n.1667G>A		non_coding_transcript_exon_variant	10/11	2
RADIL	ENST00000445392.5 linkuse as main transcript	c.*1827G>A		3_prime_UTR_variant, NMD_transcript_variant	14/15	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000323

AC:

AN:

185794

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

100952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000375

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000168

AC:

AN:

1427088

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

707008

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000525

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000146

Gnomad4 OTH exome

AF:

0.0000507

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000113

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

Feb 28, 2023

The c.3056G>A (p.R1019H) alteration is located in exon 14 (coding exon 13) of the RADIL gene. This alteration results from a G to A substitution at nucleotide position 3056, causing the arginine (R) at amino acid position 1019 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.38

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.72

MutPred

0.64

Loss of methylation at R1019 (P = 0.0335);

MVP

0.57

MPC

0.33

ClinPred

0.90

GERP RS

5.3

Varity_R

0.44

gMVP

0.75

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