Variant chr19-32996097-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033103.5(RHPN2):c.1349C>T(p.Ser450Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RHPN2
NM_033103.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.23

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]

RHPN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5 linkuse as main transcript	c.1349C>T	p.Ser450Phe	missense_variant	11/15	ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8 linkuse as main transcript	c.1349C>T	p.Ser450Phe	missense_variant	11/15	1	NM_033103.5	P1	Q8IUC4-1
RHPN2	ENST00000544458.6 linkuse as main transcript	n.1678C>T		non_coding_transcript_exon_variant	8/12	2
RHPN2	ENST00000585641.1 linkuse as main transcript	n.365C>T		non_coding_transcript_exon_variant	1/2	5
RHPN2	ENST00000588388.5 linkuse as main transcript	c.*886C>T		3_prime_UTR_variant, NMD_transcript_variant	10/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727148

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:

0.00000270

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

Jan 20, 2023

The c.1349C>T (p.S450F) alteration is located in exon 11 (coding exon 11) of the RHPN2 gene. This alteration results from a C to T substitution at nucleotide position 1349, causing the serine (S) at amino acid position 450 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

M_CAP

Benign

0.057

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.71

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.42

Sift

Benign

0.051

Sift4G

Uncertain

0.028

Polyphen

0.99

Vest4

0.64

MutPred

0.47

Loss of disorder (P = 0.0139);

MVP

0.63

MPC

1.1

ClinPred

0.99

GERP RS

4.9

Varity_R

0.73

gMVP

0.74

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

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