Genetic Variant CSAG1:p.Pro54Arg (chrX-152728080-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001102576.3(CSAG1):c.161C>G(p.Pro54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,208,796 control chromosomes in the GnomAD database, including 36 homozygotes. There are 698 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., 334 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 10 hom. 364 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010496974).

BP6

Variant X-152728080-G-C is Benign according to our data. Variant chrX-152728080-G-C is described in ClinVar as [Benign]. Clinvar id is 790250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1307/110812) while in subpopulation AFR AF= 0.0407 (1234/30335). AF 95% confidence interval is 0.0388. There are 26 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAG1	NM_001102576.3 link	c.161C>G	p.Pro54Arg	missense_variant	Exon 3 of 4	ENST00000452779.3	NP_001096046.2	Q6PB30-1
CSAG1	NM_153478.3 link	c.161C>G	p.Pro54Arg	missense_variant	Exon 4 of 5		NP_705611.2	Q6PB30-1
CSAG1	XM_047441858.1 link	c.161C>G	p.Pro54Arg	missense_variant	Exon 3 of 4		XP_047297814.1
CSAG1	XM_047441859.1 link	c.161C>G	p.Pro54Arg	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>G	p.Pro54Arg	missense_variant	Exon 3 of 4	1	NM_001102576.3	ENSP00000396520.2		Q6PB30-1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1291

AN:

110761

Hom.:

Cov.:

AF XY:

0.00973

AC XY:

321

AN XY:

32983

show subpopulations

Gnomad AFR

AF:

0.0402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00538

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00602

GnomAD3 exomes

AF:

0.00314

AC:

575

AN:

183295

Hom.:

AF XY:

0.00211

AC XY:

143

AN XY:

67859

show subpopulations

Gnomad AFR exome

AF:

0.0402

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.00120

AC:

1313

AN:

1097984

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

364

AN XY:

363458

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.0118

AC:

1307

AN:

110812

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

334

AN XY:

33044

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.00537

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00594

Alfa

AF:

0.000482

Hom.:

Bravo

AF:

0.0136

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.037

.;T;T

LIST_S2

Benign

0.53

T;.;T

MetaRNN

Benign

0.010

T;T;T

PROVEAN

Pathogenic

-9.0

D;D;D

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.011

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over