Variant 17-5282508-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004703.6(RABEP1):c.22T>C(p.Ser8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000271 in 1,106,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RABEP1
NM_004703.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.217

Variant links:

Genes affected

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RABEP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053823113).

BP6

Variant 17-5282508-T-C is Benign according to our data. Variant chr17-5282508-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2534515.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6 link	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 18	ENST00000537505.6	NP_004694.2	Q15276-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RABEP1	ENST00000537505.6 link	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 18	1	NM_004703.6	ENSP00000445408.2	Q15276-1
RABEP1	ENST00000341923.10 link	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 17	1		ENSP00000339569.6	Q15276-2
RABEP1	ENST00000575475.2 link	n.187T>C		non_coding_transcript_exon_variant	Exon 1 of 14	1
RABEP1	ENST00000575991.1 link	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 3	4		ENSP00000459550.1	I3L2B8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000271

AC:

AN:

1106078

Hom.:

Cov.:

AF XY:

0.00000189

AC XY:

AN XY:

530224

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000214

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0062

T;T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.18

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.28

.;N;N

REVEL

Benign

0.086

Sift

Benign

0.28

.;T;T

Sift4G

Benign

0.34

.;T;T

Polyphen

0.0

.;B;B

Vest4

0.072, 0.075

MutPred

0.13

Loss of phosphorylation at S8 (P = 0.0217);Loss of phosphorylation at S8 (P = 0.0217);Loss of phosphorylation at S8 (P = 0.0217);

MVP

0.18

ClinPred

0.096

GERP RS

-0.053

Varity_R

0.11

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over