rs376593652

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003881.4(CCN5):c.236A>T(p.Gln79Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000507 in 1,577,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

CCN5
NM_003881.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

Publications

0 publications found

Variant links:

Genes affected

CCN5 (HGNC:12770): (cellular communication network factor 5) This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like (CT) domain. The encoded protein lacks the CT domain which is implicated in dimerization and heparin binding. It is 72% identical to the mouse protein at the amino acid level. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Its expression in colon tumors is reduced while the other two WISP members are overexpressed in colon tumors. It is expressed at high levels in bone tissue, and may play an important role in modulating bone turnover. [provided by RefSeq, Jul 2008]

CCN5 links:

KCNK15-AS1 (HGNC:49901): (KCNK15 and WISP2 antisense RNA 1)

KCNK15-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31461602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003881.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCN5	NM_003881.4	MANE Select	c.236A>T	p.Gln79Leu	missense	Exon 2 of 4	NP_003872.1	O76076-1
CCN5	NM_001323370.2		c.236A>T	p.Gln79Leu	missense	Exon 3 of 5	NP_001310299.1	O76076-1
CCN5	NM_001323369.2		c.236A>T	p.Gln79Leu	missense	Exon 2 of 3	NP_001310298.1	O76076-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCN5	ENST00000190983.5	TSL:1 MANE Select	c.236A>T	p.Gln79Leu	missense	Exon 2 of 4	ENSP00000190983.4	O76076-1
CCN5	ENST00000372865.4	TSL:1	c.236A>T	p.Gln79Leu	missense	Exon 2 of 3	ENSP00000361956.4	O76076-2
CCN5	ENST00000372868.6	TSL:3	c.236A>T	p.Gln79Leu	missense	Exon 3 of 5	ENSP00000361959.2	O76076-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000107

AC:

AN:

187164

AF XY:

0.00000976

show subpopulations

Gnomad AFR exome

AF:

0.0000898

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:

0.0000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000491

AC:

AN:

1425132

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33112

American (AMR)

AF:

0.00

AC:

AN:

40348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25478

East Asian (EAS)

AF:

0.00

AC:

AN:

38688

South Asian (SAS)

AF:

0.00

AC:

AN:

83028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00000637

AC:

AN:

1099644

Other (OTH)

AF:

0.00

AC:

AN:

59262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000168

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

0.083

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

M_CAP

Benign

0.075

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

PhyloP100

6.1

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.37

MVP

0.35

MPC

0.25

ClinPred

0.78

GERP RS

4.4

Varity_R

0.31

gMVP

0.42

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over