X-152728188-C-G

Variant names:

• chrX-152728188-C-G
• rs1556830818
• NM_001102576.3:c.53G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001102576.3(CSAG1):​c.53G>C​(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,209,446 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. 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. R18W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000036 (0 hom. 9 hem.)
• Consequence: CSAG1 NM_001102576.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10019699).
• BS2: High Hemizygotes in GnomAdExome4 at 9 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.53G>C	p.Arg18Pro	missense	Exon 3 of 4	NP_001096046.2	Q6PB30-1
	CSAG1	NM_153478.3		c.53G>C	p.Arg18Pro	missense	Exon 4 of 5	NP_705611.2	Q6PB30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSAG1	ENST00000452779.3	TSL:1 MANE Select	c.53G>C	p.Arg18Pro	missense	Exon 3 of 4	ENSP00000396520.2	Q6PB30-1
	CSAG1	ENST00000370287.7	TSL:1	c.53G>C	p.Arg18Pro	missense	Exon 4 of 5	ENSP00000359310.3	Q6PB30-1
	CSAG1	ENST00000370291.6	TSL:1	c.53G>C	p.Arg18Pro	missense	Exon 4 of 4	ENSP00000359314.2	Q6PB30-2

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111567 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183295 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000364 AC: 40 AN: 1097828 Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 9 AN XY: 363304

African (AFR) AF: 0.00 AC: 0 AN: 26387

American (AMR) AF: 0.00 AC: 0 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.0000463 AC: 39 AN: 841788

Other (OTH) AF: 0.0000217 AC: 1 AN: 46079

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111618 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33816

African (AFR) AF: 0.00 AC: 0 AN: 30695

American (AMR) AF: 0.00 AC: 0 AN: 10550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3560

South Asian (SAS) AF: 0.00 AC: 0 AN: 2604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6037

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53100

Other (OTH) AF: 0.00 AC: 0 AN: 1530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.31
DEOGEN2	Benign	0.0036	T
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.10	T
PhyloP100		-0.14
PROVEAN	Benign	-0.68	N
Sift	Benign	0.20	T
Sift4G	Benign	0.17	T
Vest4		0.23
gMVP		0.025

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1556830818; hg19: chrX-151908814;