17-40188883-A-G

Position:

• chr17-40188883-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016339.6(RAPGEFL1):​c.851A>G​(p.Gln284Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAPGEFL1 NM_016339.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.11

Genes affected

RAPGEFL1 (HGNC:17428): (Rap guanine nucleotide exchange factor like 1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and nervous system development. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAPGEFL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072753996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEFL1	NM_016339.6	c.851A>G	p.Gln284Arg	missense_variant	5/15	ENST00000620260.6	NP_057423.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEFL1	ENST00000620260.6	c.851A>G	p.Gln284Arg	missense_variant	5/15	1	NM_016339.6	ENSP00000479735.1
RAPGEFL1	ENST00000456989.6	c.398A>G	p.Gln133Arg	missense_variant	5/15	1		ENSP00000394530.2
RAPGEFL1	ENST00000544503.5	c.380A>G	p.Gln127Arg	missense_variant	5/15	2		ENSP00000438631.1
RAPGEFL1	ENST00000264644.10	c.233A>G	p.Gln78Arg	missense_variant	5/15	5		ENSP00000264644.5
RAPGEFL1	ENST00000543876.5	c.233A>G	p.Gln78Arg	missense_variant	5/6	4		ENSP00000440226.1
RAPGEFL1	ENST00000538981.1	c.233A>G	p.Gln78Arg	missense_variant	4/4	2		ENSP00000441059.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

research

Prostate Cancer Research Center, Institute of Biosciences and Medical Technology, University of Tampere

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.0060	.;T;T;.;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	T;T;T;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.073	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.82	N;N;N;.;.;N
REVEL	Benign	0.077
Sift	Benign	0.24	T;T;T;.;.;T
Sift4G	Benign	0.44	T;T;T;T;T;T
Vest4		0.11
MutPred		0.19		.;.;.;.;Gain of MoRF binding (P = 0.0503);.;
MVP		0.043
ClinPred		0.59	D
GERP RS		4.3
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs864622033; hg19: chr17-38345135; COSMIC: COSV52862579; COSMIC: COSV52862579;