Variant X-16862958-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002893.4(RBBP7):c.304G>A(p.Gly102Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,208,760 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

RBBP7
NM_002893.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

RBBP7 (HGNC:9890): (RB binding protein 7, chromatin remodeling factor) This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

RBBP7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP7	NM_002893.4 linkuse as main transcript	c.304G>A	p.Gly102Ser	missense_variant	3/12	ENST00000380087.7	NP_002884.1	Q16576-1Q6FHQ0
RBBP7	NM_001198719.2 linkuse as main transcript	c.436G>A	p.Gly146Ser	missense_variant	3/12		NP_001185648.1	Q16576-2
RBBP7	XM_047442291.1 linkuse as main transcript	c.436G>A	p.Gly146Ser	missense_variant	3/12		XP_047298247.1
RBBP7	XM_047442292.1 linkuse as main transcript	c.304G>A	p.Gly102Ser	missense_variant	3/12		XP_047298248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP7	ENST00000380087.7 linkuse as main transcript	c.304G>A	p.Gly102Ser	missense_variant	3/12	1	NM_002893.4	ENSP00000369427.3		Q16576-1

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111667

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33829

show subpopulations

Gnomad AFR

AF:

0.000130

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097093

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362499

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000358

AC:

AN:

111667

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33829

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Oct 07, 2024

The c.436G>A (p.G146S) alteration is located in exon 3 (coding exon 3) of the RBBP7 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the glycine (G) at amino acid position 146 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

0.20

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;.;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;T;D

M_CAP

Pathogenic

0.67

MetaRNN

Pathogenic

0.78

D;D;D;D

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.9

M;.;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.6

D;D;N;D

REVEL

Uncertain

0.45

Sift

Benign

0.060

T;T;T;T

Sift4G

Uncertain

0.054

T;T;T;.

Polyphen

0.030

B;.;B;.

Vest4

0.84

MutPred

0.33

Loss of catalytic residue at G102 (P = 0.0015);.;Loss of catalytic residue at G102 (P = 0.0015);.;

MVP

0.99

MPC

1.7

ClinPred

0.97

GERP RS

5.8

Varity_R

0.71

gMVP

0.81

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