Variant X-152727810-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.221C>T(p.Thr74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 111,729 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: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

CSAG1
NM_001102576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.274

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=0.1274837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CSAG1	NM_001102576.3 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	4/4	ENST00000452779.3	NP_001096046.2
CSAG1	NM_153478.3 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	5/5		NP_705611.2
CSAG1	XM_047441858.1 linkuse as main transcript	c.272C>T	p.Thr91Ile	missense_variant	4/4		XP_047297814.1
CSAG1	XM_047441859.1 linkuse as main transcript	c.272C>T	p.Thr91Ile	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.221C>T	p.Thr74Ile	missense_variant	4/4	1	NM_001102576.3	ENSP00000396520	A2	Q6PB30-1
CSAG1	ENST00000370287.7 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	5/5	1		ENSP00000359310	A2	Q6PB30-1
CSAG1	ENST00000370291.6 linkuse as main transcript	c.*209C>T		3_prime_UTR_variant	4/4	1		ENSP00000359314	P4	Q6PB30-2
CSAG1	ENST00000361211.9 linkuse as main transcript	c.*144C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000354898

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111729

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33919

show subpopulations

Gnomad AFR

AF:

0.0000326

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183249

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67849

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000182

AC:

AN:

1097610

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363148

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111729

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33919

show subpopulations

Gnomad4 AFR

AF:

0.0000326

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Nov 14, 2023

The c.221C>T (p.T74I) 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 221, causing the threonine (T) at amino acid position 74 to be replaced by an isoleucine (I). 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

0.36

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.037

T;T

LIST_S2

Benign

0.53

.;T

MetaRNN

Benign

0.13

T;T

PROVEAN

Uncertain

-4.0

D;D

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.049

D;D

Vest4

0.12

gMVP

0.024

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