chr10-60889144-C-T

Variant summary

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

The NM_014836.5(RHOBTB1):​c.524G>A​(p.Arg175Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,612,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RHOBTB1
NM_014836.5 missense

Scores

1
13
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
Variant links:
Genes affected
RHOBTB1 (HGNC:18738): (Rho related BTB domain containing 1) The protein encoded by this gene belongs to the Rho family of the small GTPase superfamily. It contains a GTPase domain, a proline-rich region, a tandem of 2 BTB (broad complex, tramtrack, and bric-a-brac) domains, and a conserved C-terminal region. The protein plays a role in small GTPase-mediated signal transduction and the organization of the actin filament system. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

Genome browser will be placed here

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 UniProt
RHOBTB1NM_014836.5 linkuse as main transcriptc.524G>A p.Arg175Gln missense_variant 6/11 ENST00000337910.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHOBTB1ENST00000337910.10 linkuse as main transcriptc.524G>A p.Arg175Gln missense_variant 6/111 NM_014836.5 P1
RHOBTB1ENST00000357917.4 linkuse as main transcriptc.524G>A p.Arg175Gln missense_variant 7/122 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250268
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135226
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460810
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
726558
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000965
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
Alfa
AF:
0.0000662
Hom.:
0
Bravo
AF:
0.0000189

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 GeneticsNov 20, 2023The c.524G>A (p.R175Q) alteration is located in exon 7 (coding exon 4) of the RHOBTB1 gene. This alteration results from a G to A substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 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
Uncertain
0.41
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.61
D;D
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
.;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
0.97
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.054
T;T
Polyphen
0.76
P;P
Vest4
0.72
MVP
0.83
MPC
2.2
ClinPred
0.90
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1157759221; hg19: chr10-62648902; API