Variant 7-66775288-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000284957.9(RABGEF1):c.241C>T(p.Leu81Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RABGEF1
ENST00000284957.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78

Variant links:

Genes affected

RABGEF1 (HGNC:17676): (RAB guanine nucleotide exchange factor 1) RABGEF1 forms a complex with rabaptin-5 (RABPT5; MIM 603616) that is required for endocytic membrane fusion, and it serves as a specific guanine nucleotide exchange factor (GEF) for RAB5 (RAB5A; MIM 179512) (Horiuchi et al., 1997 [PubMed 9323142]).[supplied by OMIM, Mar 2010]

RABGEF1 links:

ENSG00000284461 (HGNC:):

ENSG00000284461 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3497481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGEF1	NM_014504.3 linkuse as main transcript	c.241C>T	p.Leu81Phe	missense_variant	3/9	ENST00000284957.9	NP_055319.1	Q9UJ41-2A0A024RDL6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RABGEF1	ENST00000284957.9 linkuse as main transcript	c.241C>T	p.Leu81Phe	missense_variant	3/9	1	NM_014504.3	ENSP00000284957.4	Q9UJ41-2
ENSG00000284461	ENST00000503687.2 linkuse as main transcript	n.*76C>T		non_coding_transcript_exon_variant	6/13	2		ENSP00000421074.1	E9PHB8
ENSG00000284461	ENST00000503687.2 linkuse as main transcript	n.*76C>T		3_prime_UTR_variant	6/13	2		ENSP00000421074.1	E9PHB8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250958

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135646

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727128

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Apr 08, 2024

The c.241C>T (p.L81F) alteration is located in exon 3 (coding exon 2) of the RABGEF1 gene. This alteration results from a C to T substitution at nucleotide position 241, causing the leucine (L) at amino acid position 81 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

.;.;.;.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

T;.;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.8

N;N;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.074

T;T;T;.;T

Sift4G

Benign

0.19

T;T;T;T;T

Vest4

0.50

MutPred

0.22

Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);.;.;

MVP

0.79

MPC

0.53

ClinPred

0.80

GERP RS

5.6

gMVP

0.24

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

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