chrX-155116113-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001018055.3(BRCC3):c.605T>C(p.Val202Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000912 in 1,206,226 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000096 ( 0 hom. 31 hem. )

Consequence

BRCC3
NM_001018055.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.54

Publications

1 publications found

Variant links:

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]

BRCC3 links:

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]

MTCP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18838665).

BS2

High AC in GnomAd4 at 5 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRCC3	NM_001018055.3	MANE Select	c.605T>C	p.Val202Ala	missense	Exon 8 of 11	NP_001018065.1	P46736-2
BRCC3	NM_024332.4		c.680T>C	p.Val227Ala	missense	Exon 9 of 12	NP_077308.1	P46736-1
BRCC3	NM_001242640.2		c.608T>C	p.Val203Ala	missense	Exon 8 of 11	NP_001229569.1	P46736-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRCC3	ENST00000330045.12	TSL:1 MANE Select	c.605T>C	p.Val202Ala	missense	Exon 8 of 11	ENSP00000328641.7	P46736-2
BRCC3	ENST00000369462.5	TSL:1	c.680T>C	p.Val227Ala	missense	Exon 9 of 12	ENSP00000358474.1	P46736-1
BRCC3	ENST00000340647.8	TSL:2	c.608T>C	p.Val203Ala	missense	Exon 8 of 11	ENSP00000344103.4	P46736-3

Frequencies

GnomAD3 genomes

AF:

0.0000449

AC:

AN:

111477

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000943

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

177195

AF XY:

0.0000157

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000959

AC:

105

AN:

1094749

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

360661

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26331

American (AMR)

AF:

0.00

AC:

AN:

34995

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19320

East Asian (EAS)

AF:

0.00

AC:

AN:

30151

South Asian (SAS)

AF:

0.00

AC:

AN:

53657

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3998

European-Non Finnish (NFE)

AF:

0.000121

AC:

102

AN:

839957

Other (OTH)

AF:

0.0000653

AC:

AN:

45940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000449

AC:

AN:

111477

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33659

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30611

American (AMR)

AF:

0.00

AC:

AN:

10532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3535

South Asian (SAS)

AF:

0.00

AC:

AN:

2661

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6027

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000943

AC:

AN:

53046

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.048

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.65

M_CAP

Benign

0.0072

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

PhyloP100

2.5

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.030

REVEL

Benign

0.031

Sift

Benign

0.55

Sift4G

Benign

0.63

Polyphen

0.0040

Vest4

0.28

MutPred

0.39

Loss of sheet (P = 0.0315)

MVP

0.82

MPC

1.5

ClinPred

0.18

GERP RS

3.6

Varity_R

0.15

gMVP

0.94

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over