NM_001018055.3:c.493-404C>T

Variant names:

• chrX-155090380-C-T
• rs184669955
• NM_001018055.3:c.493-404C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: Benign. The variant received -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 VariationId is 223596.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 726 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018055.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRCC3	NM_001018055.3	MANE Select	c.493-404C>T		intron	N/A	NP_001018065.1	P46736-2
	BRCC3	NM_024332.4		c.493-404C>T		intron	N/A	NP_077308.1	P46736-1
	BRCC3	NM_001242640.2		c.496-404C>T		intron	N/A	NP_001229569.1	P46736-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRCC3	ENST00000330045.12	TSL:1 MANE Select	c.493-404C>T		intron	N/A	ENSP00000328641.7	P46736-2
	BRCC3	ENST00000369462.5	TSL:1	c.493-404C>T		intron	N/A	ENSP00000358474.1	P46736-1
	BRCC3	ENST00000340647.8	TSL:2	c.496-404C>T		intron	N/A	ENSP00000344103.4	P46736-3

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 726 AN: 112453 Hom.: 3 Cov.: 23

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

African (AFR) AF: 0.00123 AC: 38 AN: 30997

American (AMR) AF: 0.00346 AC: 37 AN: 10698

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 57 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3603

South Asian (SAS) AF: 0.000368 AC: 1 AN: 2721

European-Finnish (FIN) AF: 0.0229 AC: 140 AN: 6110

Middle Eastern (MID) AF: 0.00922 AC: 2 AN: 217

European-Non Finnish (NFE) AF: 0.00828 AC: 441 AN: 53284

Other (OTH) AF: 0.00648 AC: 10 AN: 1544

Alfa AF: 0.00751 Hom.: 47

Bravo AF: 0.00566

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.1
DANN	Benign	0.88
PhyloP100		-0.18
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: rs184669955; hg19: chrX-154318655;