Variant 16-24562016-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006910.5(RBBP6):c.1144C>T(p.Pro382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,613,470 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 0.00025 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

RBBP6
NM_006910.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.954

Variant links:

Genes affected

RBBP6 (HGNC:9889): (RB binding protein 6, ubiquitin ligase) The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. In various human cancers, pRB suppresses cellular proliferation and is inactivated. Cell cycle-dependent phosphorylation regulates the activity of pRB. This gene encodes a protein which binds to underphosphorylated but not phosphorylated pRB. Multiple alternatively spliced transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RBBP6 links:

RBBP6 (HGNC:):

RBBP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029624224).

BS2

High AC in GnomAd4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP6	NM_006910.5 linkuse as main transcript	c.1144C>T	p.Pro382Ser	missense_variant	10/18	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4 linkuse as main transcript	c.1144C>T	p.Pro382Ser	missense_variant	10/17		NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10 linkuse as main transcript	c.1144C>T	p.Pro382Ser	missense_variant	10/18	1	NM_006910.5	ENSP00000317872.4		Q7Z6E9-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152122

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251152

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000235

AC:

344

AN:

1461230

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000281

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000250

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74440

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:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000413

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

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

Nov 15, 2024

The c.1144C>T (p.P382S) alteration is located in exon 10 (coding exon 10) of the RBBP6 gene. This alteration results from a C to T substitution at nucleotide position 1144, causing the proline (P) at amino acid position 382 to be replaced by a serine (S). 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

0.060

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;T;.;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.030

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

.;N;N;.;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.6

D;D;N;.;D

REVEL

Benign

0.066

Sift

Benign

0.087

T;T;T;.;T

Sift4G

Benign

0.90

T;T;T;.;T

Polyphen

0.10, 0.0, 0.16

.;B;B;.;B

Vest4

0.12, 0.10, 0.13

MVP

0.23

MPC

0.19

ClinPred

0.041

GERP RS

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.52

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.

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