chrX-16845071-A-T

Variant names:

• chrX-16845071-A-T
• rs141936185
• NM_002893.4:c.1242T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002893.4(RBBP7):​c.1242T>A​(p.Asp414Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,511 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
• Consequence: RBBP7 NM_002893.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.931
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14304078).

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.1242T>A	p.Asp414Glu	missense	Exon 12 of 12	NP_002884.1	Q6FHQ0
	RBBP7	NM_001198719.2		c.1374T>A	p.Asp458Glu	missense	Exon 12 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.1242T>A	p.Asp414Glu	missense	Exon 12 of 12	ENSP00000369427.3	Q16576-1
	RBBP7	ENST00000380084.8	TSL:2	c.1374T>A	p.Asp458Glu	missense	Exon 12 of 12	ENSP00000369424.4	Q16576-2
	RBBP7	ENST00000967933.1		c.1335T>A	p.Asp445Glu	missense	Exon 13 of 13	ENSP00000637992.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112511 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000645

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

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181967 AF XY: 0.00

Gnomad AFR exome AF: 0.0000762

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112511 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34655

African (AFR) AF: 0.0000645 AC: 2 AN: 30989

American (AMR) AF: 0.00 AC: 0 AN: 10627

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3605

South Asian (SAS) AF: 0.00 AC: 0 AN: 2741

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53306

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

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	Benign	0.076
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N
PhyloP100		0.93
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.10
Sift	Benign	0.87	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.21		Gain of glycosylation at S413 (P = 0.0712)
MVP		0.81
MPC		1.2
ClinPred		0.22	T
GERP RS		3.2
Varity_R		0.16
gMVP		0.64
Mutation Taster		=73/27	polymorphism

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

dbSNP: rs141936185; hg19: chrX-16863194;