Genetic Variant CSAG1:p.Val68Ile (chrX-152727829-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001102576.3(CSAG1):c.202G>A(p.Val68Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000308 in 1,209,008 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 104 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00031 ( 0 hom. 95 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.39

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027163029).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSAG1	NM_001102576.3 link	c.202G>A	p.Val68Ile	missense_variant	Exon 4 of 4	ENST00000452779.3	NP_001096046.2	Q6PB30-1
CSAG1	NM_153478.3 link	c.202G>A	p.Val68Ile	missense_variant	Exon 5 of 5		NP_705611.2	Q6PB30-1
CSAG1	XM_047441858.1 link	c.253G>A	p.Val85Ile	missense_variant	Exon 4 of 4		XP_047297814.1
CSAG1	XM_047441859.1 link	c.253G>A	p.Val85Ile	missense_variant	Exon 4 of 4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSAG1	ENST00000452779.3 link	c.202G>A	p.Val68Ile	missense_variant	Exon 4 of 4	1	NM_001102576.3	ENSP00000396520.2		Q6PB30-1

Frequencies

GnomAD3 genomes

AF:

0.000260

AC:

AN:

111539

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

AN XY:

33697

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.000433

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000196

AC:

AN:

183228

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

67838

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000437

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:

0.000245

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000313

AC:

343

AN:

1097469

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

AN XY:

363057

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000366

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000260

AC:

AN:

111539

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

AN XY:

33697

show subpopulations

Gnomad4 AFR

AF:

0.000131

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000433

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.000314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.030

DANN

Benign

0.30

DEOGEN2

Benign

0.0013

T;T

LIST_S2

Benign

0.28

.;T

MetaRNN

Benign

0.027

T;T

PROVEAN

Benign

0.16

N;N

Sift

Benign

0.80

T;T

Sift4G

Benign

0.54

T;T

Vest4

0.029

gMVP

0.0024

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over