Variant X-152728101-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001102576.3(CSAG1):c.140C>T(p.Ser47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,208,851 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.928

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1130425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSAG1	NM_001102576.3 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	3/4	ENST00000452779.3	NP_001096046.2	Q6PB30-1
CSAG1	NM_153478.3 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	4/5		NP_705611.2	Q6PB30-1
CSAG1	XM_047441858.1 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	3/4		XP_047297814.1
CSAG1	XM_047441859.1 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	3/4		XP_047297815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSAG1	ENST00000452779.3 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	3/4	1	NM_001102576.3	ENSP00000396520.2		Q6PB30-1

Frequencies

GnomAD3 genomes

AF:

0.00000902

AC:

AN:

110891

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33091

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:

0.000283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183299

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67863

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000289

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000902

AC:

AN:

110891

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33091

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

May 03, 2023

The c.140C>T (p.S47F) alteration is located in exon 4 (coding exon 2) of the CSAG1 gene. This alteration results from a C to T substitution at nucleotide position 140, causing the serine (S) at amino acid position 47 to be replaced by a phenylalanine (F). 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

Uncertain

0.37

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.8

DANN

Benign

0.91

DEOGEN2

Benign

0.031

.;T;T

LIST_S2

Benign

0.51

T;.;T

MetaRNN

Benign

0.11

T;T;T

PROVEAN

Pathogenic

-4.6

D;D;D

Sift

Benign

0.24

T;T;T

Sift4G

Uncertain

0.027

D;D;D

Vest4

0.14

gMVP

0.018

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