NM_001102576.3:c.161C>G

Variant names:

• chrX-152728080-G-C
• rs1556830729
• NM_001102576.3:c.161C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170
• 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 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.161C>G	p.Pro54Arg	missense	Exon 3 of 4	NP_001096046.2	Q6PB30-1
	CSAG1	NM_153478.3		c.161C>G	p.Pro54Arg	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.161C>G	p.Pro54Arg	missense	Exon 3 of 4	ENSP00000396520.2	Q6PB30-1
	CSAG1	ENST00000370287.7	TSL:1	c.161C>G	p.Pro54Arg	missense	Exon 4 of 5	ENSP00000359310.3	Q6PB30-1
	CSAG1	ENST00000370291.6	TSL:1	c.161C>G	p.Pro54Arg	missense	Exon 4 of 4	ENSP00000359314.2	Q6PB30-2

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1291 AN: 110761 Hom.: 26 Cov.: 22

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

GnomAD2 exomes AF: 0.00314 AC: 575 AN: 183295 AF XY: 0.00211

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 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.: 10 Cov.: 33 AF XY: 0.00100 AC XY: 364 AN XY: 363458

African (AFR) AF: 0.0389 AC: 1027 AN: 26394

American (AMR) AF: 0.00173 AC: 61 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

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

South Asian (SAS) AF: 0.0000739 AC: 4 AN: 54118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00266 AC: 11 AN: 4131

European-Non Finnish (NFE) AF: 0.000109 AC: 92 AN: 841938

Other (OTH) AF: 0.00256 AC: 118 AN: 46085

GnomAD4 genome AF: 0.0118 AC: 1307 AN: 110812 Hom.: 26 Cov.: 22 AF XY: 0.0101 AC XY: 334 AN XY: 33044

African (AFR) AF: 0.0407 AC: 1234 AN: 30335

American (AMR) AF: 0.00537 AC: 56 AN: 10424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3518

South Asian (SAS) AF: 0.00 AC: 0 AN: 2556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5979

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000151 AC: 8 AN: 52950

Other (OTH) AF: 0.00594 AC: 9 AN: 1515

Alfa AF: 0.000482 Hom.: 1

Bravo AF: 0.0136

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.037	T
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.010	T
PhyloP100		-0.017
PROVEAN	Pathogenic	-9.0	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	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

Other links and lift over

dbSNP: rs1556830729; hg19: chrX-151908922; COSMIC: COSV99057046;