chr17-76340464-T-C

Variant names:

• chr17-76340464-T-C
• rs11077813
• NM_002766.3:c.290+4207A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002766.3(PRPSAP1):​c.290+4207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,394 control chromosomes in the GnomAD database, including 4,284 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4284 hom., cov: 32)
• Consequence: PRPSAP1 NM_002766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPSAP1	NM_002766.3	MANE Select	c.290+4207A>G		intron	N/A	NP_002757.2
	PRPSAP1	NM_001330503.2		c.-19-8029A>G		intron	N/A	NP_001317432.1
	PRPSAP1	NM_001366236.2		c.-20+4207A>G		intron	N/A	NP_001353165.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPSAP1	ENST00000446526.8	TSL:1 MANE Select	c.290+4207A>G		intron	N/A	ENSP00000414624.2
	PRPSAP1	ENST00000324684.8	TSL:2	c.-20+4207A>G		intron	N/A	ENSP00000314973.4
	PRPSAP1	ENST00000435555.6	TSL:5	c.-20+4207A>G		intron	N/A	ENSP00000392838.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31271 AN: 151276 Hom.: 4287 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31261 AN: 151394 Hom.: 4284 Cov.: 32 AF XY: 0.212 AC XY: 15697 AN XY: 74000

African (AFR) AF: 0.0538 AC: 2198 AN: 40828

American (AMR) AF: 0.193 AC: 2936 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3468

East Asian (EAS) AF: 0.573 AC: 2967 AN: 5178

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4810

European-Finnish (FIN) AF: 0.333 AC: 3515 AN: 10566

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17278 AN: 67992

Other (OTH) AF: 0.193 AC: 405 AN: 2102

Alfa AF: 0.223 Hom.: 10732

Bravo AF: 0.189

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.096
DANN	Benign	0.76
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs11077813; hg19: chr17-74336545;