rs17856308

Positions:

• chr1-41010181-G-A
• chr1-41010181-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001905.4(CTPS1):​c.1712G>A​(p.Ser571Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S571I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTPS1 NM_001905.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.27

Genes affected

CTPS1 (HGNC:2519): (CTP synthase 1) This gene encodes an enzyme responsible for the catalytic conversion of UTP (uridine triphosphate) to CTP (cytidine triphospate). This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. Activity of this proten is important in the immune system, and loss of function of this gene has been associated with immunodeficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CTPS1 (HGNC:):

ACMG classification

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=0.25343168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTPS1	NM_001905.4	c.1712G>A	p.Ser571Asn	missense_variant	18/19	ENST00000650070.2	NP_001896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTPS1	ENST00000650070.2	c.1712G>A	p.Ser571Asn	missense_variant	18/19		NM_001905.4	ENSP00000497602.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461532 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 727090

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;.;.;D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.3	M;M;M;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.65	N;.;.;N;.
REVEL	Benign	0.19
Sift	Benign	0.063	T;.;.;T;.
Sift4G	Benign	0.11	T;.;.;T;.
Polyphen		0.98	D;D;D;D;.
Vest4		0.49
MutPred		0.13		Loss of phosphorylation at S571 (P = 0.0058);Loss of phosphorylation at S571 (P = 0.0058);Loss of phosphorylation at S571 (P = 0.0058);Loss of phosphorylation at S571 (P = 0.0058);.;
MVP		0.68
MPC		2.0
ClinPred		0.89	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs17856308; hg19: chr1-41475853;