Variant X-152727829-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001102576.3(CSAG1):c.202G>C(p.Val68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,209,085 control chromosomes in the GnomAD database, including 1 homozygotes. There are 136 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00029 ( 1 hom. 128 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051531434).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CSAG1	NM_001102576.3 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	4/4	ENST00000452779.3	NP_001096046.2
CSAG1	NM_153478.3 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	5/5		NP_705611.2
CSAG1	XM_047441858.1 linkuse as main transcript	c.253G>C	p.Val85Leu	missense_variant	4/4		XP_047297814.1
CSAG1	XM_047441859.1 linkuse as main transcript	c.253G>C	p.Val85Leu	missense_variant	4/4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSAG1	ENST00000452779.3 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	4/4	1	NM_001102576.3	ENSP00000396520	A2	Q6PB30-1
CSAG1	ENST00000370287.7 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	5/5	1		ENSP00000359310	A2	Q6PB30-1
CSAG1	ENST00000370291.6 linkuse as main transcript	c.*190G>C		3_prime_UTR_variant	4/4	1		ENSP00000359314	P4	Q6PB30-2
CSAG1	ENST00000361211.9 linkuse as main transcript	c.*125G>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000354898

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111539

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

33697

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

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:

0.000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

183228

Hom.:

AF XY:

0.000398

AC XY:

AN XY:

67838

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000839

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.000294

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000294

AC:

323

AN:

1097546

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

128

AN XY:

363086

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:

0.000776

Gnomad4 FIN exome

AF:

0.0000987

Gnomad4 NFE exome

AF:

0.000304

Gnomad4 OTH exome

AF:

0.000413

GnomAD4 genome

AF:

0.000206

AC:

AN:

111539

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

33697

show subpopulations

Gnomad4 AFR

AF:

0.0000653

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.000212

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.202G>C (p.V68L) alteration is located in exon 5 (coding exon 3) of the CSAG1 gene. This alteration results from a G to C substitution at nucleotide position 202, causing the valine (V) at amino acid position 68 to be replaced by a leucine (L). 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

0.14

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.061

DANN

Benign

0.24

DEOGEN2

Benign

0.033

T;T

LIST_S2

Benign

0.36

.;T

MetaRNN

Benign

0.052

T;T

PROVEAN

Benign

-0.71

N;N

Sift

Benign

0.11

T;T

Sift4G

Benign

0.76

T;T

Vest4

0.073

gMVP

0.0045

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over