rs2271590

Variant names:

• chr4-107653949-C-T
• rs2271590
• NM_005443.5:c.1102-323G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005443.5. 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
	PAPSS1	NM_005443.5	MANE Select	c.1102-323G>A		intron	N/A	NP_005434.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS1	ENST00000265174.5	TSL:1 MANE Select	c.1102-323G>A		intron	N/A	ENSP00000265174.4
	PAPSS1	ENST00000511304.5	TSL:3	n.794-323G>A		intron	N/A

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

African (AFR) AF: 0.0761 AC: 3161 AN: 41554

American (AMR) AF: 0.236 AC: 3602 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1896 AN: 5160

South Asian (SAS) AF: 0.151 AC: 729 AN: 4830

European-Finnish (FIN) AF: 0.238 AC: 2513 AN: 10574

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14480 AN: 68000

Other (OTH) AF: 0.210 AC: 443 AN: 2114

Alfa AF: 0.187 Hom.: 393

Bravo AF: 0.186

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.075
DANN	Benign	0.75
PhyloP100		-4.6
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: rs2271590; hg19: chr4-108575105;