Variant 7-4799461-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018059.5(RADIL):c.3145G>A(p.Gly1049Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RADIL
NM_018059.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RADIL	NM_018059.5 linkuse as main transcript	c.3145G>A	p.Gly1049Ser	missense_variant	15/15	ENST00000399583.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RADIL	ENST00000399583.4 linkuse as main transcript	c.3145G>A	p.Gly1049Ser	missense_variant	15/15	5	NM_018059.5	P1	Q96JH8-4
RADIL	ENST00000472999.5 linkuse as main transcript	n.1169G>A		non_coding_transcript_exon_variant	5/5	1
RADIL	ENST00000473130.5 linkuse as main transcript	n.1756G>A		non_coding_transcript_exon_variant	11/11	2
RADIL	ENST00000445392.5 linkuse as main transcript	c.*1916G>A		3_prime_UTR_variant, NMD_transcript_variant	15/15	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249432

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000555

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Sep 28, 2022

The c.3145G>A (p.G1049S) alteration is located in exon 15 (coding exon 14) of the RADIL gene. This alteration results from a G to A substitution at nucleotide position 3145, causing the glycine (G) at amino acid position 1049 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.94

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

REVEL

Benign

0.17

Sift

Benign

0.31

Sift4G

Benign

0.50

Polyphen

0.91

Vest4

0.57

MutPred

0.36

Gain of phosphorylation at G1049 (P = 0.0652);

MVP

0.47

MPC

0.22

ClinPred

0.42

GERP RS

4.9

Varity_R

0.10

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: -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