X-155071541-TGGTGCAGGC-T

Variant names:

• chrX-155071541-TGGTGCAGGC-T
• rs782702164
• NM_001018055.3:c.27_35delGCAGGCGGT

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 3P and 6B. PM4 PP3 BP6_Moderate BS2

The NM_001018055.3(BRCC3):​c.27_35delGCAGGCGGT​(p.Gln10_Val12del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,203,958 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 218 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., 9 hem., cov: 23)
  • Exomes 𝑓: 0.00062 (0 hom. 209 hem.)
• Consequence: BRCC3 NM_001018055.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.64
• 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: Likely_benign. The variant received -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001018055.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant X-155071541-TGGTGCAGGC-T is Benign according to our data. Variant chrX-155071541-TGGTGCAGGC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 38 AD,XL 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.27_35delGCAGGCGGT	p.Gln10_Val12del	disruptive_inframe_deletion	Exon 1 of 11	NP_001018065.1	P46736-2
	BRCC3	NM_024332.4		c.27_35delGCAGGCGGT	p.Gln10_Val12del	disruptive_inframe_deletion	Exon 1 of 12	NP_077308.1	P46736-1
	BRCC3	NM_001242640.2		c.27_35delGCAGGCGGT	p.Gln10_Val12del	disruptive_inframe_deletion	Exon 1 of 11	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.27_35delGCAGGCGGT	p.Gln10_Val12del	disruptive_inframe_deletion	Exon 1 of 11	ENSP00000328641.7	P46736-2
	BRCC3	ENST00000369462.5	TSL:1	c.27_35delGCAGGCGGT	p.Gln10_Val12del	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000358474.1	P46736-1
	BRCC3	ENST00000340647.8	TSL:2	c.27_35delGCAGGCGGT	p.Gln10_Val12del	disruptive_inframe_deletion	Exon 1 of 11	ENSP00000344103.4	P46736-3

Frequencies

GnomAD3 genomes AF: 0.000338 AC: 38 AN: 112374 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000928

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000566

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000312 AC: 51 AN: 163208 AF XY: 0.000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000770

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000206

Gnomad NFE exome AF: 0.000650

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000616 AC: 672 AN: 1091542 Hom.: 0 AF XY: 0.000583 AC XY: 209 AN XY: 358234

African (AFR) AF: 0.0000380 AC: 1 AN: 26289

American (AMR) AF: 0.0000872 AC: 3 AN: 34422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19262

East Asian (EAS) AF: 0.000468 AC: 14 AN: 29937

South Asian (SAS) AF: 0.0000189 AC: 1 AN: 52945

European-Finnish (FIN) AF: 0.000151 AC: 6 AN: 39826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4113

European-Non Finnish (NFE) AF: 0.000759 AC: 637 AN: 838895

Other (OTH) AF: 0.000218 AC: 10 AN: 45853

GnomAD4 genome AF: 0.000338 AC: 38 AN: 112416 Hom.: 0 Cov.: 23 AF XY: 0.000260 AC XY: 9 AN XY: 34668

African (AFR) AF: 0.000161 AC: 5 AN: 31078

American (AMR) AF: 0.0000926 AC: 1 AN: 10794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2771

European-Finnish (FIN) AF: 0.000163 AC: 1 AN: 6148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000566 AC: 30 AN: 53014

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.000109 Hom.: 1

Bravo AF: 0.000397

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6
Mutation Taster		=195/5	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782702164; hg19: chrX-154299816;