Genetic Variant CSPG5:p.Pro499Arg (chr3-47569114-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001206943.2(CSPG5):c.1496C>G(p.Pro499Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,591,378 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P499L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CSPG5
NM_001206943.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.35

Publications

0 publications found

Variant links:

Genes affected

CSPG5 (HGNC:2467): (chondroitin sulfate proteoglycan 5) The protein encoded by this gene is a proteoglycan that may function as a neural growth and differentiation factor. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

CSPG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206943.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSPG5	NM_006574.4	MANE Select	c.1458+38C>G		intron	N/A	NP_006565.2	O95196-2
CSPG5	NM_001206943.2		c.1496C>G	p.Pro499Arg	missense	Exon 4 of 5	NP_001193872.1	O95196-1
CSPG5	NM_001206945.2		c.1082C>G	p.Pro361Arg	missense	Exon 4 of 5	NP_001193874.1	B7Z2E0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSPG5	ENST00000383738.6	TSL:1	c.1496C>G	p.Pro499Arg	missense	Exon 4 of 5	ENSP00000373244.2	O95196-1
CSPG5	ENST00000264723.9	TSL:1 MANE Select	c.1458+38C>G		intron	N/A	ENSP00000264723.4	O95196-2
CSPG5	ENST00000456150.5	TSL:1	c.1044+38C>G		intron	N/A	ENSP00000392096.1	O95196-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1439182

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

715054

show subpopulations

African (AFR)

AF:

0.0000312

AC:

AN:

32088

American (AMR)

AF:

0.00

AC:

AN:

41056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24734

East Asian (EAS)

AF:

0.00

AC:

AN:

38420

South Asian (SAS)

AF:

0.00

AC:

AN:

82702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1102366

Other (OTH)

AF:

0.0000168

AC:

AN:

59424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

3.4

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

REVEL

Benign

0.26

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.55

MutPred

0.57

Gain of MoRF binding (P = 6e-04)

MVP

0.37

MPC

1.6

ClinPred

0.94

GERP RS

4.7

Varity_R

0.37

gMVP

0.39

Mutation Taster

=72/28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over