NM_004057.3:c.188G>A

Variant names:

• chrX-16654457-G-A
• rs1932771775
• NM_004057.3:c.188G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_004057.3(S100G):​c.188G>A​(p.Gly63Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000367 in 1,090,512 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: S100G NM_004057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100G	NM_004057.3	MANE Select	c.188G>A	p.Gly63Glu	missense	Exon 3 of 3	NP_004048.1	P29377
	CTPS2	NM_175859.3	MANE Select	c.1296+13057C>T		intron	N/A	NP_787055.1	Q9NRF8
	CTPS2	NM_001144002.2		c.1296+13057C>T		intron	N/A	NP_001137474.1	Q9NRF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100G	ENST00000380200.3	TSL:1 MANE Select	c.188G>A	p.Gly63Glu	missense	Exon 3 of 3	ENSP00000369547.3	P29377
	CTPS2	ENST00000359276.9	TSL:1 MANE Select	c.1296+13057C>T		intron	N/A	ENSP00000352222.4	Q9NRF8
	CTPS2	ENST00000380241.7	TSL:1	c.1296+13057C>T		intron	N/A	ENSP00000369590.3	Q9NRF8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000367 AC: 4 AN: 1090512 Hom.: 0 Cov.: 26 AF XY: 0.00000561 AC XY: 2 AN XY: 356218

African (AFR) AF: 0.0000382 AC: 1 AN: 26192

American (AMR) AF: 0.0000287 AC: 1 AN: 34869

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19282

East Asian (EAS) AF: 0.00 AC: 0 AN: 30055

South Asian (SAS) AF: 0.00 AC: 0 AN: 53332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 836417

Other (OTH) AF: 0.00 AC: 0 AN: 45797

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.78	D
PhyloP100		4.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.1	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.72		Gain of disorder (P = 0.045)
MVP		0.18
MPC		0.89
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.85
gMVP		0.71
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1932771775; hg19: chrX-16672580;