NM_001102576.3:c.122G>C

Variant names:

• chrX-152728119-C-G
• NM_001102576.3:c.122G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001102576.3(CSAG1):​c.122G>C​(p.Arg41Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CSAG1 NM_001102576.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3592494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAG1	NM_001102576.3	c.122G>C	p.Arg41Pro	missense_variant	Exon 3 of 4	ENST00000452779.3	NP_001096046.2
CSAG1	NM_153478.3	c.122G>C	p.Arg41Pro	missense_variant	Exon 4 of 5		NP_705611.2
CSAG1	XM_047441858.1	c.122G>C	p.Arg41Pro	missense_variant	Exon 3 of 4		XP_047297814.1
CSAG1	XM_047441859.1	c.122G>C	p.Arg41Pro	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	c.122G>C	p.Arg41Pro	missense_variant	Exon 3 of 4	1	NM_001102576.3	ENSP00000396520.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.122G>C (p.R41P) alteration is located in exon 4 (coding exon 2) of the CSAG1 gene. This alteration results from a G to C substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a proline (P). 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	Uncertain	0.42
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.037	.;T;T
LIST_S2	Benign	0.57	T;.;T
MetaRNN	Benign	0.36	T;T;T
PROVEAN	Pathogenic	-7.0	D;D;D
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.35
gMVP		0.034

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-151908883;