chr19-32991938-C-T

Variant summary

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

The NM_033103.5(RHPN2):​c.1529G>A​(p.Arg510Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,830 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

RHPN2
NM_033103.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57
Variant links:
Genes affected
RHPN2 (HGNC:19974): (rhophilin Rho GTPase binding protein 2) This gene encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. The encoded protein binds both GTP- and GDP-bound RhoA and GTP-bound RhoB and may be involved in the organization of the actin cytoskeleton. [provided by RefSeq, Apr 2009]

Genome browser will be placed here

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=0.18551186).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RHPN2NM_033103.5 linkuse as main transcriptc.1529G>A p.Arg510Gln missense_variant 13/15 ENST00000254260.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHPN2ENST00000254260.8 linkuse as main transcriptc.1529G>A p.Arg510Gln missense_variant 13/151 NM_033103.5 P1Q8IUC4-1
RHPN2ENST00000544458.6 linkuse as main transcriptn.1858G>A non_coding_transcript_exon_variant 10/122
RHPN2ENST00000591502.1 linkuse as main transcriptn.208G>A non_coding_transcript_exon_variant 1/22
RHPN2ENST00000588388.5 linkuse as main transcriptc.*1066G>A 3_prime_UTR_variant, NMD_transcript_variant 12/142

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
250936
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135644
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000506
AC:
74
AN:
1461648
Hom.:
0
Cov.:
31
AF XY:
0.0000605
AC XY:
44
AN XY:
727132
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:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000164
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsAug 05, 2023The c.1529G>A (p.R510Q) alteration is located in exon 13 (coding exon 13) of the RHPN2 gene. This alteration results from a G to A substitution at nucleotide position 1529, causing the arginine (R) at amino acid position 510 to be replaced by a glutamine (Q). 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
0.099
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T
Eigen
Benign
0.13
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.099
Sift
Benign
0.14
T
Sift4G
Benign
0.18
T
Polyphen
0.82
P
Vest4
0.35
MVP
0.41
MPC
0.49
ClinPred
0.15
T
GERP RS
3.1
Varity_R
0.13
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs750379907; hg19: chr19-33482844; API