rs2271590

chr4-107653949-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005443.5(PAPSS1):c.1102-323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,182 control chromosomes in the GnomAD database, including 2,977 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 0.18 (2977 hom., cov: 32)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.63

Genes affected

PAPSS1 (HGNC:8603): (3'-phosphoadenosine 5'-phosphosulfate synthase 1) Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS1	NM_005443.5	c.1102-323G>A		intron_variant		ENST00000265174.5
PAPSS1	XM_011532400.3	c.1039-323G>A		intron_variant
PAPSS1	XM_011532401.2	c.1039-323G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS1	ENST00000265174.5	c.1102-323G>A		intron_variant		1	NM_005443.5	P1
PAPSS1	ENST00000511304.5	n.794-323G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27855 AN: 152064 Hom.: 2970 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.183 AC: 27874 AN: 152182 Hom.: 2977 Cov.: 32 AF XY: 0.185 AC XY: 13768 AN XY: 74388

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.210

Alfa AF: 0.191 Hom.: 389

Bravo AF: 0.186

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.075
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs2271590; hg19: chr4-108575105;