dbSNP rs1556830729: CSAG1:p.Pro54Leu (chrX-152728080-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001102576.3(CSAG1):c.161C>T(p.Pro54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,208,797 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 79 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 41 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 0 hom. 38 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18171942).

BS2

High Hemizygotes in GnomAd4 at 41 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAG1	NM_001102576.3 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 3 of 4	ENST00000452779.3	NP_001096046.2	Q6PB30-1
CSAG1	NM_153478.3 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 4 of 5		NP_705611.2	Q6PB30-1
CSAG1	XM_047441858.1 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 3 of 4		XP_047297814.1
CSAG1	XM_047441859.1 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 3 of 4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSAG1	ENST00000452779.3 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 3 of 4	1	NM_001102576.3	ENSP00000396520.2		Q6PB30-1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

141

AN:

110762

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

32984

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000384

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:

0.00

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.000431

AC:

AN:

183295

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

67859

show subpopulations

Gnomad AFR exome

AF:

0.00585

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

140

AN:

1097984

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

363458

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.00129

AC:

143

AN:

110813

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

33045

show subpopulations

Gnomad4 AFR

AF:

0.00455

Gnomad4 AMR

AF:

0.000384

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000660

Alfa

AF:

0.0000877

Hom.:

Bravo

AF:

0.00145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.037

.;T;T

LIST_S2

Benign

0.64

T;.;T

MetaRNN

Benign

0.18

T;T;T

PROVEAN

Pathogenic

-10

D;D;D

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.012

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over