NM_006910.5:c.879G>C

Variant names:

• chr16-24561643-G-C
• NM_006910.5:c.879G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006910.5(RBBP6):​c.879G>C​(p.Glu293Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBBP6 NM_006910.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.39
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057524443).
• BP6: Variant 16-24561643-G-C is Benign according to our data. Variant chr16-24561643-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2480967.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP6	NM_006910.5	c.879G>C	p.Glu293Asp	missense_variant	Exon 9 of 18	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4	c.879G>C	p.Glu293Asp	missense_variant	Exon 9 of 17		NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10	c.879G>C	p.Glu293Asp	missense_variant	Exon 9 of 18	1	NM_006910.5	ENSP00000317872.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 06, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.074
DANN	Benign	0.92
DEOGEN2	Benign	0.33	.;.;T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.81	T;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.058	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.15	.;.;N;N;.;N
PhyloP100		-2.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N;N;N;N;.;N
REVEL	Benign	0.26
Sift	Benign	0.20	T;T;T;T;.;T
Sift4G	Benign	0.18	T;T;T;T;.;T
Polyphen		0.0, 0.054	.;.;B;B;.;B
Vest4		0.12, 0.14, 0.14
MutPred		0.30		.;Loss of disorder (P = 0.186);Loss of disorder (P = 0.186);Loss of disorder (P = 0.186);.;Loss of disorder (P = 0.186);
MVP		0.50
MPC		1.8
ClinPred		0.12	T
GERP RS		-6.7
Varity_R		0.044
gMVP		0.74

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

Other links and lift over

hg19: chr16-24572964;