X-152728200-A-G

Position:

• chrX-152728200-A-G

Variant summary

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

The NM_001102576.3(CSAG1):​c.41T>C​(p.Leu14Pro) 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. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CSAG1 NM_001102576.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.727

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=0.32186192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSAG1	NM_001102576.3	c.41T>C	p.Leu14Pro	missense_variant	3/4	ENST00000452779.3	NP_001096046.2
CSAG1	NM_153478.3	c.41T>C	p.Leu14Pro	missense_variant	4/5		NP_705611.2
CSAG1	XM_047441858.1	c.41T>C	p.Leu14Pro	missense_variant	3/4		XP_047297814.1
CSAG1	XM_047441859.1	c.41T>C	p.Leu14Pro	missense_variant	3/4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSAG1	ENST00000452779.3	c.41T>C	p.Leu14Pro	missense_variant	3/4	1	NM_001102576.3	ENSP00000396520	A2
CSAG1	ENST00000370287.7	c.41T>C	p.Leu14Pro	missense_variant	4/5	1		ENSP00000359310	A2
CSAG1	ENST00000370291.6	c.41T>C	p.Leu14Pro	missense_variant	4/4	1		ENSP00000359314	P4
CSAG1	ENST00000361211.9	c.48T>C	p.Pro16=	synonymous_variant, NMD_transcript_variant	3/4	1		ENSP00000354898

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.41T>C (p.L14P) alteration is located in exon 4 (coding exon 2) of the CSAG1 gene. This alteration results from a T to C substitution at nucleotide position 41, causing the leucine (L) at amino acid position 14 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	Benign	0.18
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.047	.;T;T
LIST_S2	Benign	0.41	T;.;T
MetaRNN	Benign	0.32	T;T;T
PROVEAN	Benign	-2.1	N;N;N
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.46
gMVP		0.11

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-151908802;