rs2726670

Positions:

• chr4-107615229-G-A
• chr4-107615229-G-T

Variant summary

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

The NM_005443.5(PAPSS1):​c.1737-842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,886 control chromosomes in the GnomAD database, including 7,594 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 0.32 (7594 hom., cov: 31)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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]

PAPSS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.1737-842C>T		intron_variant		ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.1674-842C>T		intron_variant			XP_011530702.1
PAPSS1	XM_011532401.2	c.1674-842C>T		intron_variant			XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5	c.1737-842C>T		intron_variant		1	NM_005443.5	ENSP00000265174.4
PAPSS1	ENST00000514815.1	n.174+16402C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47804 AN: 151768 Hom.: 7571 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.315 AC: 47863 AN: 151886 Hom.: 7594 Cov.: 31 AF XY: 0.313 AC XY: 23210 AN XY: 74214

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.355

Alfa AF: 0.287 Hom.: 3395

Bravo AF: 0.327

Asia WGS AF: 0.335 AC: 1164 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2726670; hg19: chr4-108536385;