rs895744

Variant names:

• chrX-155117516-G-T
• rs895744
• NM_001018055.3:c.724+762G>T

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCC3	NM_001018055.3	c.724+762G>T		intron_variant	Intron 9 of 10	ENST00000330045.12	NP_001018065.1
BRCC3	NM_024332.4	c.799+762G>T		intron_variant	Intron 10 of 11		NP_077308.1
BRCC3	NM_001242640.2	c.727+762G>T		intron_variant	Intron 9 of 10		NP_001229569.1
BRCC3	XM_005274751.5	c.802+762G>T		intron_variant	Intron 10 of 11		XP_005274808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRCC3	ENST00000330045.12	c.724+762G>T		intron_variant	Intron 9 of 10	1	NM_001018055.3	ENSP00000328641.7

Frequencies

GnomAD3 genomes AF: 0.593 AC: 65082 AN: 109702 Hom.: 15081 Cov.: 22

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

African (AFR) AF: 0.295 AC: 8911 AN: 30212

American (AMR) AF: 0.624 AC: 6423 AN: 10296

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 1815 AN: 2617

East Asian (EAS) AF: 0.724 AC: 2504 AN: 3459

South Asian (SAS) AF: 0.533 AC: 1382 AN: 2591

European-Finnish (FIN) AF: 0.765 AC: 4344 AN: 5675

Middle Eastern (MID) AF: 0.720 AC: 154 AN: 214

European-Non Finnish (NFE) AF: 0.726 AC: 38159 AN: 52537

Other (OTH) AF: 0.624 AC: 922 AN: 1477

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
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs895744; hg19: chrX-154345791;