rs1803757

Variant names:

• chr17-76332272-C-A
• rs1803757
• NM_002766.3:c.454G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-76332272-C-A
• chr17-76332272-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002766.3(PRPSAP1):​c.454G>T​(p.Ala152Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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. A152T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PRPSAP1 NM_002766.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 1 publications found

Genes affected

PRPSAP1 (HGNC:9466): (phosphoribosyl pyrophosphate synthetase associated protein 1) Enables identical protein binding activity. Predicted to be involved in 5-phosphoribose 1-diphosphate biosynthetic process and purine nucleotide biosynthetic process. Predicted to be part of ribose phosphate diphosphokinase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21959352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002766.3. 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
	PRPSAP1	NM_002766.3	MANE Select	c.454G>T	p.Ala152Ser	missense	Exon 4 of 10	NP_002757.2	Q14558-2
	PRPSAP1	NM_001330503.2		c.145G>T	p.Ala49Ser	missense	Exon 3 of 9	NP_001317432.1	B4DP31
	PRPSAP1	NM_001366236.2		c.145G>T	p.Ala49Ser	missense	Exon 4 of 10	NP_001353165.1	B4DP31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPSAP1	ENST00000446526.8	TSL:1 MANE Select	c.454G>T	p.Ala152Ser	missense	Exon 4 of 10	ENSP00000414624.2	Q14558-2
	PRPSAP1	ENST00000908407.1		c.454G>T	p.Ala152Ser	missense	Exon 4 of 11	ENSP00000578466.1
	PRPSAP1	ENST00000922958.1		c.454G>T	p.Ala152Ser	missense	Exon 4 of 10	ENSP00000593017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251314 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461782 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	0.0059	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.45	T
PhyloP100		3.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.30
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.016	B
Vest4		0.35
MVP		0.61
MPC		0.35
ClinPred		0.28	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.43
Mutation Taster		=68/32	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: rs1803757; hg19: chr17-74328353;