Variant X-152728087-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001102576.3(CSAG1):c.154T>C(p.Ser52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,985 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000064 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00900

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021209478).

BP6

Variant X-152728087-A-G is Benign according to our data. Variant chrX-152728087-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2603660.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CSAG1	NM_001102576.3 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	3/4	ENST00000452779.3	NP_001096046.2
CSAG1	NM_153478.3 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	4/5		NP_705611.2
CSAG1	XM_047441858.1 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	3/4		XP_047297814.1
CSAG1	XM_047441859.1 linkuse as main transcript	c.154T>C	p.Ser52Pro	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.154T>C	p.Ser52Pro	missense_variant	3/4	1	NM_001102576.3	ENSP00000396520	A2	Q6PB30-1
CSAG1	ENST00000370287.7 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	4/5	1		ENSP00000359310	A2	Q6PB30-1
CSAG1	ENST00000370291.6 linkuse as main transcript	c.154T>C	p.Ser52Pro	missense_variant	4/4	1		ENSP00000359314	P4	Q6PB30-2
CSAG1	ENST00000361211.9 linkuse as main transcript	c.*77T>C		3_prime_UTR_variant, NMD_transcript_variant	3/4	1		ENSP00000354898

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

110318

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32640

FAILED QC

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183290

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67858

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000721

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:

0.00000638

AC:

AN:

1097985

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363465

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:

0.0000370

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000906

AC:

AN:

110318

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32640

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

DANN

Benign

0.37

DEOGEN2

Benign

0.00082

.;T;T

LIST_S2

Benign

0.24

T;.;T

MetaRNN

Benign

0.021

T;T;T

PROVEAN

Benign

3.3

N;N;N

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Vest4

0.030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.0029

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