1-205094959-G-T

Variant names:

• chr1-205094959-G-T
• NM_005057.4:c.1502C>A

Variant summary

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

The NM_005057.4(RBBP5):​c.1502C>A​(p.Pro501Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBBP5 NM_005057.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.71

Genes affected

RBBP5 (HGNC:9888): (RB binding protein 5, histone lysine methyltransferase complex subunit) This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. The encoded protein binds directly to retinoblastoma protein, which regulates cell proliferation. It interacts preferentially with the underphosphorylated retinoblastoma protein via the E1A-binding pocket B. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP5	NM_005057.4	c.1502C>A	p.Pro501Gln	missense_variant	Exon 13 of 14	ENST00000264515.11	NP_005048.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP5	ENST00000264515.11	c.1502C>A	p.Pro501Gln	missense_variant	Exon 13 of 14	1	NM_005057.4	ENSP00000264515.6
RBBP5	ENST00000367164.1	c.1474+28C>A		intron_variant	Intron 13 of 13	1		ENSP00000356132.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1502C>A (p.P501Q) alteration is located in exon 13 (coding exon 13) of the RBBP5 gene. This alteration results from a C to A substitution at nucleotide position 1502, causing the proline (P) at amino acid position 501 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.27
Sift	Benign	0.093	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.16		Gain of MoRF binding (P = 0.0264);
MVP		0.50
MPC		0.24
ClinPred		0.77	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -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: chr1-205064087;