Genetic Variant NM_016339.6:c.1439C>T (chr17-40191419-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016339.6(RAPGEFL1):c.1439C>T(p.Ala480Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAPGEFL1
NM_016339.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

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 links:

ENSG00000295930 (HGNC:):

ENSG00000295930 links:

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ACMG classification

Classification was made for transcript

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=0.22430605).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAPGEFL1	NM_016339.6	MANE Select	c.1439C>T	p.Ala480Val	missense	Exon 9 of 15	NP_057423.2	A0A087WVW6
RAPGEFL1	NM_001303533.2		c.986C>T	p.Ala329Val	missense	Exon 9 of 15	NP_001290462.1	Q9UHV5-3
RAPGEFL1	NM_001303534.3		c.968C>T	p.Ala323Val	missense	Exon 9 of 15	NP_001290463.1	F5H2D5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAPGEFL1	ENST00000620260.6	TSL:1 MANE Select	c.1439C>T	p.Ala480Val	missense	Exon 9 of 15	ENSP00000479735.1	A0A087WVW6
RAPGEFL1	ENST00000456989.6	TSL:1	c.986C>T	p.Ala329Val	missense	Exon 9 of 15	ENSP00000394530.2	Q9UHV5-3
RAPGEFL1	ENST00000544503.5	TSL:2	c.968C>T	p.Ala323Val	missense	Exon 9 of 15	ENSP00000438631.1	F5H2D5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722554

African (AFR)

AF:

0.00

AC:

AN:

33058

American (AMR)

AF:

0.00

AC:

AN:

43968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25944

East Asian (EAS)

AF:

0.00

AC:

AN:

39334

South Asian (SAS)

AF:

0.00

AC:

AN:

85516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4432

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110214

Other (OTH)

AF:

0.00

AC:

AN:

59928

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0097

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.014

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

PhyloP100

1.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.69

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.15

Vest4

0.36

MutPred

0.54

Loss of catalytic residue at A480 (P = 0.3572)

MVP

0.15

ClinPred

0.84

GERP RS

5.0

gMVP

0.55

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over