Variant chr5-95748377-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000379982.8(RHOBTB3):c.460A>C(p.Ser154Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000621 in 1,613,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

RHOBTB3
ENST00000379982.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.18

Variant links:

Genes affected

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RHOBTB3 links:

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=0.1263138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RHOBTB3	NM_014899.4 linkuse as main transcript	c.460A>C	p.Ser154Arg	missense_variant	4/12	ENST00000379982.8	NP_055714.3
RHOBTB3	XM_011543279.3 linkuse as main transcript	c.460A>C	p.Ser154Arg	missense_variant	4/11		XP_011541581.1
RHOBTB3	XM_017009237.2 linkuse as main transcript	c.-123A>C		5_prime_UTR_variant	4/12		XP_016864726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOBTB3	ENST00000379982.8 linkuse as main transcript	c.460A>C	p.Ser154Arg	missense_variant	4/12	1	NM_014899.4	ENSP00000369318	P1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.000691

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000446

AC:

112

AN:

251170

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000599

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000636

AC:

929

AN:

1460908

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

439

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000984

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:

0.000763

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.000480

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.000578

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000478

AC:

EpiCase

AF:

0.000547

EpiControl

AF:

0.000534

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

Dec 19, 2023

The c.460A>C (p.S154R) alteration is located in exon 4 (coding exon 4) of the RHOBTB3 gene. This alteration results from a A to C substitution at nucleotide position 460, causing the serine (S) at amino acid position 154 to be replaced by an arginine (R). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.84

.;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.034

D;.

Polyphen

0.94

.;P

Vest4

0.60

MutPred

0.29

.;Loss of disorder (P = 0.0926);

MVP

0.92

MPC

1.2

ClinPred

0.20

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.35

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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