X-16852835-A-C

Position:

• chrX-16852835-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002893.4(RBBP7):​c.799T>G​(p.Leu267Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RBBP7 NM_002893.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

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 (HGNC:):

ACMG classification

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=0.13983321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP7	NM_002893.4	c.799T>G	p.Leu267Val	missense_variant	7/12	ENST00000380087.7	NP_002884.1
RBBP7	NM_001198719.2	c.931T>G	p.Leu311Val	missense_variant	7/12		NP_001185648.1
RBBP7	XM_047442291.1	c.931T>G	p.Leu311Val	missense_variant	7/12		XP_047298247.1
RBBP7	XM_047442292.1	c.799T>G	p.Leu267Val	missense_variant	7/12		XP_047298248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP7	ENST00000380087.7	c.799T>G	p.Leu267Val	missense_variant	7/12	1	NM_002893.4	ENSP00000369427.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

The c.931T>G (p.L311V) alteration is located in exon 7 (coding exon 7) of the RBBP7 gene. This alteration results from a T to G substitution at nucleotide position 931, causing the leucine (L) at amino acid position 311 to be replaced by a valine (V). 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	0.051
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T;.;.;.;.
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N;.;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.49	N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.59	T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;.
Polyphen		0.0	B;.;B;.;.
Vest4		0.17
MutPred		0.23		Loss of catalytic residue at L267 (P = 0.0627);.;.;.;.;
MVP		0.60
MPC		1.3
ClinPred		0.23	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.19

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: chrX-16870958;