17-40184653-C-G

Variant names:

• chr17-40184653-C-G
• rs1330182244
• NM_016339.6:c.808C>G

Variant summary

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

The NM_016339.6(RAPGEFL1):​c.808C>G​(p.Gln270Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q270K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RAPGEFL1 NM_016339.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

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]

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=0.21958351).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016339.6. 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
	RAPGEFL1	NM_016339.6	MANE Select	c.808C>G	p.Gln270Glu	missense	Exon 4 of 15	NP_057423.2	A0A087WVW6
	RAPGEFL1	NM_001303533.2		c.355C>G	p.Gln119Glu	missense	Exon 4 of 15	NP_001290462.1	Q9UHV5-3
	RAPGEFL1	NM_001303534.3		c.337C>G	p.Gln113Glu	missense	Exon 4 of 15	NP_001290463.1	F5H2D5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEFL1	ENST00000620260.6	TSL:1 MANE Select	c.808C>G	p.Gln270Glu	missense	Exon 4 of 15	ENSP00000479735.1	A0A087WVW6
	RAPGEFL1	ENST00000456989.6	TSL:1	c.355C>G	p.Gln119Glu	missense	Exon 4 of 15	ENSP00000394530.2	Q9UHV5-3
	RAPGEFL1	ENST00000544503.5	TSL:2	c.337C>G	p.Gln113Glu	missense	Exon 4 of 15	ENSP00000438631.1	F5H2D5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.81	T
PhyloP100		4.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.11
Sift	Benign	0.066	T
Sift4G	Benign	0.094	T
Vest4		0.59
MutPred		0.32		Gain of loop (P = 0.1069)
MVP		0.043
ClinPred		0.72	D
GERP RS		5.3
gMVP		0.17

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: rs1330182244; hg19: chr17-38340905;