Variant 10-60878035-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014836.5(RHOBTB1):c.1599G>T(p.Lys533Asn) 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 1,459,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RHOBTB1
NM_014836.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

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]

RHOBTB1 links:

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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	Protein	UniProt
RHOBTB1	NM_014836.5 linkuse as main transcript	c.1599G>T	p.Lys533Asn	missense_variant	8/11	ENST00000337910.10	NP_055651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RHOBTB1	ENST00000337910.10 linkuse as main transcript	c.1599G>T	p.Lys533Asn	missense_variant	8/11	1	NM_014836.5	ENSP00000338671	P1
RHOBTB1	ENST00000357917.4 linkuse as main transcript	c.1599G>T	p.Lys533Asn	missense_variant	9/12	2		ENSP00000350595	P1
RHOBTB1	ENST00000483488.1 linkuse as main transcript	n.282G>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248016

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133844

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459710

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725990

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 16, 2024

The c.1599G>T (p.K533N) alteration is located in exon 9 (coding exon 6) of the RHOBTB1 gene. This alteration results from a G to T substitution at nucleotide position 1599, causing the lysine (K) at amino acid position 533 to be replaced by an asparagine (N). 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

0.51

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.25

Sift

Benign

0.074

T;T

Sift4G

Uncertain

0.026

D;D

Polyphen

0.87

P;P

Vest4

0.54

MutPred

0.59

Loss of methylation at K533 (P = 0.0106);Loss of methylation at K533 (P = 0.0106);

MVP

0.77

MPC

0.78

ClinPred

0.73

GERP RS

4.3

Varity_R

0.28

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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