16-24562046-T-G

Variant summary

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

The NM_006910.5(RBBP6):ā€‹c.1174T>Gā€‹(p.Ser392Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

RBBP6
NM_006910.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.758
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]

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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=0.108707786).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBBP6NM_006910.5 linkuse as main transcriptc.1174T>G p.Ser392Ala missense_variant 10/18 ENST00000319715.10 NP_008841.2
RBBP6NM_018703.4 linkuse as main transcriptc.1174T>G p.Ser392Ala missense_variant 10/17 NP_061173.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RBBP6ENST00000319715.10 linkuse as main transcriptc.1174T>G p.Ser392Ala missense_variant 10/181 NM_006910.5 ENSP00000317872.4 Q7Z6E9-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460526
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726620
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 GeneticsSep 22, 2022The c.1174T>G (p.S392A) alteration is located in exon 10 (coding exon 10) of the RBBP6 gene. This alteration results from a T to G substitution at nucleotide position 1174, causing the serine (S) at amino acid position 392 to be replaced by an alanine (A). 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
0.068
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;T;.;.;.
Eigen
Benign
-0.11
Eigen_PC
Benign
0.063
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.63
T;T;T;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N;N;.;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.84
N;N;N;.;N
REVEL
Benign
0.025
Sift
Uncertain
0.025
D;D;T;.;D
Sift4G
Benign
0.29
T;T;T;.;T
Polyphen
0.31, 0.30, 0.43
.;B;B;.;B
Vest4
0.20, 0.15, 0.19
MutPred
0.14
.;Loss of glycosylation at S392 (P = 0.0174);Loss of glycosylation at S392 (P = 0.0174);.;Loss of glycosylation at S392 (P = 0.0174);
MVP
0.42
MPC
0.32
ClinPred
0.43
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.065
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: chr16-24573367; API