7-4799634-G-T

Variant names:

• chr7-4799634-G-T
• rs2306921
• NM_018059.5:c.3118C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018059.5(RADIL):​c.3118C>A​(p.Leu1040Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RADIL NM_018059.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13838795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018059.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RADIL	NM_018059.5	MANE Select	c.3118C>A	p.Leu1040Met	missense	Exon 14 of 15	NP_060529.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RADIL	ENST00000399583.4	TSL:5 MANE Select	c.3118C>A	p.Leu1040Met	missense	Exon 14 of 15	ENSP00000382492.3	Q96JH8-4
	RADIL	ENST00000472999.5	TSL:1	n.1142C>A		non_coding_transcript_exon	Exon 4 of 5
	RADIL	ENST00000904466.1		c.3118C>A	p.Leu1040Met	missense	Exon 14 of 15	ENSP00000574525.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452834 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 722060

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 43544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25686

East Asian (EAS) AF: 0.00 AC: 0 AN: 39452

South Asian (SAS) AF: 0.00 AC: 0 AN: 85226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108296

Other (OTH) AF: 0.00 AC: 0 AN: 60010

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.052
Sift	Benign	0.29	T
Sift4G	Benign	0.27	T
Polyphen		0.0030	B
Vest4		0.25
MutPred		0.50		Gain of MoRF binding (P = 0.0665)
MVP		0.25
MPC		0.046
ClinPred		0.28	T
GERP RS		3.4
Varity_R		0.079
gMVP		0.34
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs2306921; hg19: chr7-4839265;