X-16654475-A-C

Position:

chrX-16654475-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2

The NM_004057.3(S100G):c.206A>C(p.Glu69Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000546 in 1,191,512 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.000031 ( 0 hom. 8 hem. )

Consequence

S100G
NM_004057.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

Variant links:

Genes affected

S100G (HGNC:1436): (S100 calcium binding protein G) This gene encodes calbindin D9K, a vitamin D-dependent calcium-binding protein. This cytosolic protein belongs to a family of calcium-binding proteins that includes calmodulin, parvalbumin, troponin C, and S100 protein. In the intestine, the protein is vitamin D-dependent and its expression correlates with calcium transport activity. The protein may increase Ca2+ absorption by buffering Ca2+ in the cytoplasm and increase ATP-dependent Ca2+ transport in duodenal basolateral membrane vesicles. [provided by RefSeq, Jul 2008]

S100G links:

CTPS2 (HGNC:2520): (CTP synthase 2) The protein encoded by this gene catalyzes the formation of CTP from UTP with the concomitant deamination of glutamine to glutamate. This protein is the rate-limiting enzyme in the synthesis of cytosine nucleotides, which play an important role in various metabolic processes and provide the precursors necessary for the synthesis of RNA and DNA. Cancer cells that exhibit increased cell proliferation also exhibit an increased activity of this encoded protein. Thus, this protein is an attractive target for selective chemotherapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CTPS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity S100G_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.883

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100G	NM_004057.3 linkuse as main transcript	c.206A>C	p.Glu69Ala	missense_variant	3/3	ENST00000380200.3	NP_004048.1
CTPS2	NM_175859.3 linkuse as main transcript	c.1296+13039T>G		intron_variant		ENST00000359276.9	NP_787055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100G	ENST00000380200.3 linkuse as main transcript	c.206A>C	p.Glu69Ala	missense_variant	3/3	1	NM_004057.3	ENSP00000369547	P1
CTPS2	ENST00000359276.9 linkuse as main transcript	c.1296+13039T>G		intron_variant		1	NM_175859.3	ENSP00000352222	P1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

112013

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34173

show subpopulations

Gnomad AFR

AF:

0.000974

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:

0.000664

GnomAD3 exomes

AF:

0.0000732

AC:

AN:

177613

Hom.:

AF XY:

0.0000481

AC XY:

AN XY:

62387

show subpopulations

Gnomad AFR exome

AF:

0.000856

Gnomad AMR exome

AF:

0.0000767

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1079499

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

345835

show subpopulations

Gnomad4 AFR exome

AF:

0.000999

Gnomad4 AMR exome

AF:

0.0000863

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000189

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000881

GnomAD4 genome

AF:

0.000277

AC:

AN:

112013

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34173

show subpopulations

Gnomad4 AFR

AF:

0.000974

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:

0.000664

Alfa

AF:

0.000340

Hom.:

Bravo

AF:

0.000416

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

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

Apr 06, 2023

The c.206A>C (p.E69A) alteration is located in exon 3 (coding exon 2) of the S100G gene. This alteration results from a A to C substitution at nucleotide position 206, causing the glutamic acid (E) at amino acid position 69 to be replaced by an alanine (A). 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

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.47

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.94

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

0.62

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.9

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.71

MVP

0.49

MPC

0.80

ClinPred

0.48

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.91

gMVP

0.81

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