NM_005610.3:c.343A>T

Variant names:

• chr1-32668257-A-T
• NM_005610.3:c.343A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005610.3(RBBP4):​c.343A>T​(p.Ile115Phe) 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: RBBP4 NM_005610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.30
• Publications: 0 publications found

Genes affected

RBBP4 (HGNC:9887): (RB binding protein 4, chromatin remodeling factor) This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. It is present in protein complexes involved in histone acetylation and chromatin assembly. It is part of the Mi-2 complex which has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation. This encoded protein is also part of co-repressor complexes, which is an integral component of transcriptional silencing. It is found among several cellular proteins that bind directly to retinoblastoma protein to regulate cell proliferation. This protein also seems to be involved in transcriptional repression of E2F-responsive genes. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005610.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP4	NM_005610.3	MANE Select	c.343A>T	p.Ile115Phe	missense	Exon 4 of 12	NP_005601.1	Q09028-1
	RBBP4	NM_001135255.2		c.340A>T	p.Ile114Phe	missense	Exon 4 of 12	NP_001128727.1	Q09028-2
	RBBP4	NM_001135256.2		c.238A>T	p.Ile80Phe	missense	Exon 4 of 12	NP_001128728.1	Q09028-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP4	ENST00000373493.10	TSL:1 MANE Select	c.343A>T	p.Ile115Phe	missense	Exon 4 of 12	ENSP00000362592.4	Q09028-1
	RBBP4	ENST00000414241.7	TSL:1	c.340A>T	p.Ile114Phe	missense	Exon 4 of 12	ENSP00000398242.3	Q09028-2
	RBBP4	ENST00000373485.5	TSL:1	c.343A>T	p.Ile115Phe	missense	Exon 4 of 12	ENSP00000362584.1	Q09028-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.012
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.3
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.28
Sift	Benign	0.37	T
Sift4G	Benign	0.43	T
Polyphen		0.0020	B
Vest4		0.63
MutPred		0.46		Gain of methylation at K114 (P = 0.0373)
MVP		0.79
MPC		2.2
ClinPred		0.83	D
GERP RS		5.5
PromoterAI		-0.019	Neutral
Varity_R		0.72
gMVP		0.91
Mutation Taster		=16/84	disease causing

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: chr1-33133858;