Variant chr9-35751277-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080496.3(RGP1):c.499G>A(p.Val167Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000014 ( 0 hom. )

Consequence

RGP1
NM_001080496.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.101267844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGP1	NM_001080496.3 linkuse as main transcript	c.499G>A	p.Val167Ile	missense_variant	6/9	ENST00000378078.5	NP_001073965.2	Q92546A8K0K1
RGP1	XR_007061382.1 linkuse as main transcript	n.640G>A		non_coding_transcript_exon_variant	6/12
RGP1	XR_007061383.1 linkuse as main transcript	n.640G>A		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.499G>A	p.Val167Ile	missense_variant	6/9	1	NM_001080496.3	ENSP00000367318.4		Q92546
RGP1	ENST00000496906.1 linkuse as main transcript	n.734G>A		non_coding_transcript_exon_variant	5/9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 08, 2024

The c.499G>A (p.V167I) alteration is located in exon 6 (coding exon 5) of the RGP1 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the valine (V) at amino acid position 167 to be replaced by an isoleucine (I). 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

0.071

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

M_CAP

Benign

0.0024

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.070

REVEL

Benign

0.078

Sift

Benign

0.53

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.17

MutPred

0.54

Loss of sheet (P = 0.0817);

MVP

0.33

MPC

0.15

ClinPred

0.10

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.16

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