16-24561938-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006910.5(RBBP6):​c.1066C>A​(p.Pro356Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,572 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: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RBBP6
NM_006910.5 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24346301).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBBP6NM_006910.5 linkc.1066C>A p.Pro356Thr missense_variant Exon 10 of 18 ENST00000319715.10 NP_008841.2
RBBP6NM_018703.4 linkc.1066C>A p.Pro356Thr missense_variant Exon 10 of 17 NP_061173.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBBP6ENST00000319715.10 linkc.1066C>A p.Pro356Thr missense_variant Exon 10 of 18 1 NM_006910.5 ENSP00000317872.4 Q7Z6E9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461572
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727128
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1066C>A (p.P356T) alteration is located in exon 10 (coding exon 10) of the RBBP6 gene. This alteration results from a C to A substitution at nucleotide position 1066, causing the proline (P) at amino acid position 356 to be replaced by a threonine (T). 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
0.35
BayesDel_addAF
Benign
0.0025
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
.;T;.;.;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
D;D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
0.97
.;L;L;.;L
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D;D;D;.;D
REVEL
Benign
0.21
Sift
Benign
0.048
D;D;D;.;D
Sift4G
Uncertain
0.016
D;D;D;.;D
Polyphen
1.0
.;D;D;.;D
Vest4
0.44, 0.43, 0.78
MutPred
0.20
.;Loss of loop (P = 0.0153);Loss of loop (P = 0.0153);.;Loss of loop (P = 0.0153);
MVP
0.45
MPC
0.22
ClinPred
0.91
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-24573259; API