Variant X-155078908-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001018055.3(BRCC3):c.403+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 353,424 control chromosomes in the GnomAD database, including 13 homozygotes. There are 547 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., 148 hem., cov: 23)

Exomes 𝑓: 0.0060 ( 11 hom. 399 hem. )

Consequence

BRCC3
NM_001018055.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.291

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-155078908-A-G is Benign according to our data. Variant chrX-155078908-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 223603.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
BRCC3	NM_001018055.3 linkuse as main transcript	c.403+205A>G	intron_variant	ENST00000330045.12	NP_001018065.1
BRCC3	NM_001242640.2 linkuse as main transcript	c.406+205A>G	intron_variant		NP_001229569.1
BRCC3	NM_024332.4 linkuse as main transcript	c.403+205A>G	intron_variant		NP_077308.1
BRCC3	XM_005274751.5 linkuse as main transcript	c.406+205A>G	intron_variant		XP_005274808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCC3	ENST00000330045.12 linkuse as main transcript	c.403+205A>G		intron_variant		1	NM_001018055.3	ENSP00000328641	P3	P46736-2

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

530

AN:

112303

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

148

AN XY:

34441

show subpopulations

Gnomad AFR

AF:

0.00136

Gnomad AMI

AF:

0.0116

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00863

Gnomad OTH

AF:

0.00132

GnomAD4 exome

AF:

0.00602

AC:

1452

AN:

241070

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

399

AN XY:

64446

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.000979

Gnomad4 ASJ exome

AF:

0.000129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00299

Gnomad4 FIN exome

AF:

0.000825

Gnomad4 NFE exome

AF:

0.00855

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00472

AC:

530

AN:

112354

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

148

AN XY:

34502

show subpopulations

Gnomad4 AFR

AF:

0.00136

Gnomad4 AMR

AF:

0.00132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00147

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00863

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00551

Hom.:

Bravo

AF:

0.00463

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, no assertion criteria provided

clinical testing

University of Washington Department of Laboratory Medicine, University of Washington

Dec 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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