Variant chrX-155071541-TGGTGCAGGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM4PP3BP6_ModerateBS2

The NM_001018055.3(BRCC3):c.27_35del(p.Gln10_Val12del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,203,958 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 218 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00062 ( 0 hom. 209 hem. )

Consequence

BRCC3
NM_001018055.3 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.64

Variant links:

Genes affected

BRCC3 (HGNC:24185): (BRCA1/BRCA2-containing complex subunit 3) This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break sites. The component encoded by this gene can specifically cleave Lys 63-linked polyubiquitin chains, and it regulates the abundance of these polyubiquitin chains in chromatin. The loss of this gene results in abnormal angiogenesis and is associated with syndromic moyamoya, a cerebrovascular angiopathy. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jun 2011]

BRCC3 links:

MTCP1 (HGNC:7423): (mature T cell proliferation 1) This gene was identified by involvement in some t(X;14) translocations associated with mature T-cell proliferations. This region has a complex gene structure, with a common promoter and 5' exon spliced to two different sets of 3' exons that encode two different proteins. This gene represents the upstream 13 kDa protein that is a member of the TCL1 family. This protein may be involved in leukemogenesis. [provided by RefSeq, Mar 2009]

MTCP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001018055.3.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

BP6

Variant X-155071541-TGGTGCAGGC-T is Benign according to our data. Variant chrX-155071541-TGGTGCAGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661872.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-155071541-TGGTGCAGGC-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BRCC3	NM_001018055.3 linkuse as main transcript	c.27_35del	p.Gln10_Val12del	inframe_deletion	1/11	ENST00000330045.12	NP_001018065.1
BRCC3	NM_001242640.2 linkuse as main transcript	c.27_35del	p.Gln10_Val12del	inframe_deletion	1/11		NP_001229569.1
BRCC3	NM_024332.4 linkuse as main transcript	c.27_35del	p.Gln10_Val12del	inframe_deletion	1/12		NP_077308.1
BRCC3	XM_005274751.5 linkuse as main transcript	c.27_35del	p.Gln10_Val12del	inframe_deletion	1/12		XP_005274808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCC3	ENST00000330045.12 linkuse as main transcript	c.27_35del	p.Gln10_Val12del	inframe_deletion	1/11	1	NM_001018055.3	ENSP00000328641	P3	P46736-2

Frequencies

GnomAD3 genomes

AF:

0.000338

AC:

AN:

112374

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

34612

show subpopulations

Gnomad AFR

AF:

0.000161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000928

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000566

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000312

AC:

AN:

163208

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

53502

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000770

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000206

Gnomad NFE exome

AF:

0.000650

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000616

AC:

672

AN:

1091542

Hom.:

AF XY:

0.000583

AC XY:

209

AN XY:

358234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000468

Gnomad4 SAS exome

AF:

0.0000189

Gnomad4 FIN exome

AF:

0.000151

Gnomad4 NFE exome

AF:

0.000759

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.000338

AC:

AN:

112416

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

34668

show subpopulations

Gnomad4 AFR

AF:

0.000161

Gnomad4 AMR

AF:

0.0000926

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000163

Gnomad4 NFE

AF:

0.000566

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

BRCC3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over