Genetic Variant NM_001102576.3:c.53G>C (chrX-152728188-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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.

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.137

Variant links:

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]

CSAG1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10019699).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAG1	NM_001102576.3 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 4	ENST00000452779.3	NP_001096046.2	Q6PB30-1
CSAG1	NM_153478.3 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 4 of 5		NP_705611.2	Q6PB30-1
CSAG1	XM_047441858.1 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 4		XP_047297814.1
CSAG1	XM_047441859.1 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSAG1	ENST00000452779.3 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 4	1	NM_001102576.3	ENSP00000396520.2	Q6PB30-1
CSAG1	ENST00000370287.7 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 4 of 5	1		ENSP00000359310.3	Q6PB30-1
CSAG1	ENST00000370291.6 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 4 of 4	1		ENSP00000359314.2	Q6PB30-2
CSAG1	ENST00000361211.9 link	n.60G>C		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000354898.5	H9KV60

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111567

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33755

show subpopulations

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

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183295

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67859

show subpopulations

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 SAS 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:

AN:

1097828

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000463

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33816

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T

LIST_S2

Benign

0.36

T;.;T

MetaRNN

Benign

0.10

T;T;T

PROVEAN

Benign

-0.68

N;N;N

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.17

T;T;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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over