Variant X-152727831-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001102576.3(CSAG1):c.200C>T(p.Pro67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000091 in 1,209,150 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000089 ( 0 hom. 39 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.118

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19006312).

BS2

High Hemizygotes in GnomAdExome4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CSAG1	NM_001102576.3 linkuse as main transcript	c.200C>T	p.Pro67Leu	missense_variant	4/4	ENST00000452779.3	NP_001096046.2
CSAG1	NM_153478.3 linkuse as main transcript	c.200C>T	p.Pro67Leu	missense_variant	5/5		NP_705611.2
CSAG1	XM_047441858.1 linkuse as main transcript	c.251C>T	p.Pro84Leu	missense_variant	4/4		XP_047297814.1
CSAG1	XM_047441859.1 linkuse as main transcript	c.251C>T	p.Pro84Leu	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.200C>T	p.Pro67Leu	missense_variant	4/4	1	NM_001102576.3	ENSP00000396520	A2	Q6PB30-1
CSAG1	ENST00000370287.7 linkuse as main transcript	c.200C>T	p.Pro67Leu	missense_variant	5/5	1		ENSP00000359310	A2	Q6PB30-1
CSAG1	ENST00000370291.6 linkuse as main transcript	c.*188C>T		3_prime_UTR_variant	4/4	1		ENSP00000359314	P4	Q6PB30-2
CSAG1	ENST00000361211.9 linkuse as main transcript	c.*123C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000354898

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

111507

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33683

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:

0.000226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000819

AC:

AN:

183254

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67848

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:

0.0000524

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000893

AC:

AN:

1097643

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

363173

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.0000903

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000108

AC:

AN:

111507

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33683

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:

0.000226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000121

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

Dec 02, 2022

The c.200C>T (p.P67L) alteration is located in exon 5 (coding exon 3) of the CSAG1 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the proline (P) at amino acid position 67 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

0.15

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.036

T;T

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.19

T;T

PROVEAN

Pathogenic

-10

D;D

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.023

D;D

Vest4

0.094

gMVP

0.019

Splicing

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