Genetic Variant CSAG1:p.Arg18Gln (chrX-152728188-C-T) – 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.53G>A(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000091 in 1,209,395 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.137

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06931281).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAG1	NM_001102576.3 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 3 of 4	ENST00000452779.3	NP_001096046.2	Q6PB30-1
CSAG1	NM_153478.3 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 4 of 5		NP_705611.2	Q6PB30-1
CSAG1	XM_047441858.1 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 3 of 4		XP_047297814.1
CSAG1	XM_047441859.1 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 3 of 4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSAG1	ENST00000452779.3 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 3 of 4	1	NM_001102576.3	ENSP00000396520.2	Q6PB30-1
CSAG1	ENST00000370287.7 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 4 of 5	1		ENSP00000359310.3	Q6PB30-1
CSAG1	ENST00000370291.6 link	c.53G>A	p.Arg18Gln	missense_variant	Exon 4 of 4	1		ENSP00000359314.2	Q6PB30-2
CSAG1	ENST00000361211.9 link	n.60G>A		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000354898.5	H9KV60

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111567

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33755

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183295

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67859

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 SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1097828

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000832

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111567

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33755

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53G>A (p.R18Q) alteration is located in exon 4 (coding exon 2) of the CSAG1 gene. This alteration results from a G to A substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.5

DANN

Benign

0.27

DEOGEN2

Benign

0.0014

.;T;T

LIST_S2

Benign

0.40

T;.;T

MetaRNN

Benign

0.069

T;T;T

PROVEAN

Benign

0.020

N;N;N

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.38

T;T;T

Vest4

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.0053

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over