rs1556830738

Variant names:

• chrX-152728087-A-G
• rs1556830738
• NM_001102576.3:c.154T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001102576.3(CSAG1):​c.154T>C​(p.Ser52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,985 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: CSAG1 NM_001102576.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021209478).
• BP6: Variant X-152728087-A-G is Benign according to our data. Variant chrX-152728087-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2603660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.154T>C	p.Ser52Pro	missense	Exon 3 of 4	NP_001096046.2	Q6PB30-1
	CSAG1	NM_153478.3		c.154T>C	p.Ser52Pro	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.154T>C	p.Ser52Pro	missense	Exon 3 of 4	ENSP00000396520.2	Q6PB30-1
	CSAG1	ENST00000370287.7	TSL:1	c.154T>C	p.Ser52Pro	missense	Exon 4 of 5	ENSP00000359310.3	Q6PB30-1
	CSAG1	ENST00000370291.6	TSL:1	c.154T>C	p.Ser52Pro	missense	Exon 4 of 4	ENSP00000359314.2	Q6PB30-2

Frequencies

GnomAD3 genomes AF: 0.00000906 AC: 1 AN: 110318 Hom.: 0 Cov.: 22

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183290 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000721

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000638 AC: 7 AN: 1097985 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 3 AN XY: 363465

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.00 AC: 0 AN: 35199

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

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30205

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54118

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841939

Other (OTH) AF: 0.00 AC: 0 AN: 46082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000521060), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000906 AC: 1 AN: 110318 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32640

African (AFR) AF: 0.00 AC: 0 AN: 30173

American (AMR) AF: 0.00 AC: 0 AN: 10382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2627

East Asian (EAS) AF: 0.00 AC: 0 AN: 3505

South Asian (SAS) AF: 0.00 AC: 0 AN: 2542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52804

Other (OTH) AF: 0.00 AC: 0 AN: 1486

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.37
DEOGEN2	Benign	0.00082	T
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.021	T
PhyloP100		-0.0090
PROVEAN	Benign	3.3	N
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.030
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.0029

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1556830738; hg19: chrX-151908915; COSMIC: COSV100767463;