X-155090380-C-T

Position:

• chrX-155090380-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001018055.3(BRCC3):​c.493-404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 112,506 control chromosomes in the GnomAD database, including 3 homozygotes. There are 244 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.0065 (3 hom., 244 hem., cov: 23)
• Consequence: BRCC3 NM_001018055.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.180

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-155090380-C-T is Benign according to our data. Variant chrX-155090380-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 223596.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCC3	NM_001018055.3	c.493-404C>T		intron_variant		ENST00000330045.12	NP_001018065.1
BRCC3	NM_001242640.2	c.496-404C>T		intron_variant			NP_001229569.1
BRCC3	NM_024332.4	c.493-404C>T		intron_variant			NP_077308.1
BRCC3	XM_005274751.5	c.496-404C>T		intron_variant			XP_005274808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCC3	ENST00000330045.12	c.493-404C>T		intron_variant		1	NM_001018055.3	ENSP00000328641	P3

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 726 AN: 112453 Hom.: 3 Cov.: 23 AF XY: 0.00704 AC XY: 244 AN XY: 34655

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00346

Gnomad ASJ AF: 0.0215

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000366

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.00840

Gnomad NFE AF: 0.00828

Gnomad OTH AF: 0.00656

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

GnomAD4 genome AF: 0.00645 AC: 726 AN: 112506 Hom.: 3 Cov.: 23 AF XY: 0.00703 AC XY: 244 AN XY: 34718

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.0215

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000368

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.00828

Gnomad4 OTH AF: 0.00648

Alfa AF: 0.00751 Hom.: 47

Bravo AF: 0.00566

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

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	-0.60
CADD	Benign	4.1
DANN	Benign	0.88

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: rs184669955; hg19: chrX-154318655;