chrX-16845836-A-AT

Variant names:

• chrX-16845836-A-AT
• NM_002893.4:c.1200dupA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_002893.4(RBBP7):​c.1200dupA​(p.Trp401MetfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RBBP7 NM_002893.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.0280
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure, X-linked, 9

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-16845836-A-AT is Pathogenic according to our data. Variant chrX-16845836-A-AT is described in ClinVar as Pathogenic. ClinVar VariationId is 3544365.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002893.4. 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
	RBBP7	NM_002893.4	MANE Select	c.1200dupA	p.Trp401MetfsTer5	frameshift	Exon 11 of 12	NP_002884.1	Q6FHQ0
	RBBP7	NM_001198719.2		c.1332dupA	p.Trp445MetfsTer5	frameshift	Exon 11 of 12	NP_001185648.1	Q16576-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP7	ENST00000380087.7	TSL:1 MANE Select	c.1200dupA	p.Trp401MetfsTer5	frameshift	Exon 11 of 12	ENSP00000369427.3	Q16576-1
	RBBP7	ENST00000380084.8	TSL:2	c.1332dupA	p.Trp445MetfsTer5	frameshift	Exon 11 of 12	ENSP00000369424.4	Q16576-2
	RBBP7	ENST00000967933.1		c.1293dupA	p.Trp432MetfsTer5	frameshift	Exon 12 of 13	ENSP00000637992.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spermatogenic failure, X-linked, 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.028

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-16863959;