Genetic Variant CSAG1:p.Pro67Leu (chrX-152727831-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

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

The NM_001102576.3(CSAG1):c.200C>T(p.Pro67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000091 in 1,209,150 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000089 ( 0 hom. 39 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.118

Publications

0 publications found

Variant links:

Genes affected

CSAG1 (HGNC:24294): (chondrosarcoma associated gene 1) This gene encodes a member of a family of tumor antigens. The protein is expressed in chondrosarcomas, but may also be expressed in normal tissues such as testis. Alternative splicing of this gene results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

CSAG1 links:

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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=0.19006312).

BS2

High Hemizygotes in GnomAdExome4 at 39 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102576.3. 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
	CSAG1	NM_001102576.3	MANE Select	c.200C>T	p.Pro67Leu	missense	Exon 4 of 4	NP_001096046.2	Q6PB30-1
	CSAG1	NM_153478.3		c.200C>T	p.Pro67Leu	missense	Exon 5 of 5	NP_705611.2	Q6PB30-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSAG1	ENST00000452779.3	TSL:1 MANE Select	c.200C>T	p.Pro67Leu	missense	Exon 4 of 4	ENSP00000396520.2	Q6PB30-1
CSAG1	ENST00000370287.7	TSL:1	c.200C>T	p.Pro67Leu	missense	Exon 5 of 5	ENSP00000359310.3	Q6PB30-1
CSAG1	ENST00000370291.6	TSL:1	c.*188C>T		3_prime_UTR	Exon 4 of 4	ENSP00000359314.2	Q6PB30-2

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

111507

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:

0.000226

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000819

AC:

AN:

183254

AF XY:

0.0000442

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:

0.0000625

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000893

AC:

AN:

1097643

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

363173

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26389

American (AMR)

AF:

0.0000284

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.000111

AC:

AN:

54117

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

40534

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.0000903

AC:

AN:

841620

Other (OTH)

AF:

0.000130

AC:

AN:

46069

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.000108

AC:

AN:

111507

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33683

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30579

American (AMR)

AF:

0.00

AC:

AN:

10528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3577

South Asian (SAS)

AF:

0.00

AC:

AN:

2607

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

53086

Other (OTH)

AF:

0.00

AC:

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000108

Hom.:

Bravo

AF:

0.000121

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

0.15

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.036

LIST_S2

Benign

0.64

MetaRNN

Benign

0.19

PhyloP100

-0.12

PROVEAN

Pathogenic

-10

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.023

Vest4

0.094

gMVP

0.019

Splicing

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

Publications

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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