Variant 9-35751401-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001080496.3(RGP1):c.623G>T(p.Cys208Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

RGP1
NM_001080496.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82

Variant links:

Genes affected

RGP1 (HGNC:21965): (RGP1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in negative regulation of cellular protein catabolic process; positive regulation of GTPase activity; and retrograde transport, endosome to Golgi. Located in cytosol and plasma membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

RGP1 links:

RGP1 (HGNC:):

RGP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGP1	NM_001080496.3 linkuse as main transcript	c.623G>T	p.Cys208Phe	missense_variant	6/9	ENST00000378078.5	NP_001073965.2	Q92546A8K0K1
RGP1	XR_007061382.1 linkuse as main transcript	n.764G>T		non_coding_transcript_exon_variant	6/12
RGP1	XR_007061383.1 linkuse as main transcript	n.764G>T		non_coding_transcript_exon_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGP1	ENST00000378078.5 linkuse as main transcript	c.623G>T	p.Cys208Phe	missense_variant	6/9	1	NM_001080496.3	ENSP00000367318.4		Q92546
RGP1	ENST00000496906.1 linkuse as main transcript	n.858G>T		non_coding_transcript_exon_variant	5/9	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Jan 22, 2024

The c.623G>T (p.C208F) alteration is located in exon 6 (coding exon 5) of the RGP1 gene. This alteration results from a G to T substitution at nucleotide position 623, causing the cysteine (C) at amino acid position 208 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

0.13

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.046

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.43

REVEL

Benign

0.20

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0020

Polyphen

0.011

Vest4

0.47

MutPred

0.83

Loss of sheet (P = 0.1158);

MVP

0.22

MPC

0.29

ClinPred

0.63

GERP RS

5.8

Varity_R

0.44

gMVP

0.90

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

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