rs895744

Positions:

• chrX-155117516-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001018055.3(BRCC3):​c.724+762G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (15081 hom., 19132 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: BRCC3 NM_001018055.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCC3	NM_001018055.3	c.724+762G>T		intron_variant		ENST00000330045.12	NP_001018065.1
BRCC3	NM_001242640.2	c.727+762G>T		intron_variant			NP_001229569.1
BRCC3	NM_024332.4	c.799+762G>T		intron_variant			NP_077308.1
BRCC3	XM_005274751.5	c.802+762G>T		intron_variant			XP_005274808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCC3	ENST00000330045.12	c.724+762G>T		intron_variant		1	NM_001018055.3	ENSP00000328641	P3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 65082 AN: 109702 Hom.: 15081 Cov.: 22 AF XY: 0.597 AC XY: 19110 AN XY: 32016

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.593 AC: 65103 AN: 109753 Hom.: 15081 Cov.: 22 AF XY: 0.596 AC XY: 19132 AN XY: 32077

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.624

Alfa AF: 0.636 Hom.: 6125

Bravo AF: 0.576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs895744; hg19: chrX-154345791;