rs2726659

Variant names:

• chr4-107644059-T-C
• rs2726659
• NM_005443.5:c.1506+743A>G

Variant summary

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

The NM_005443.5(PAPSS1):​c.1506+743A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,040 control chromosomes in the GnomAD database, including 3,210 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 0.15 (3210 hom., cov: 32)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.1506+743A>G		intron_variant	Intron 10 of 11	ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.1443+743A>G		intron_variant	Intron 10 of 11		XP_011530702.1
PAPSS1	XM_011532401.2	c.1443+743A>G		intron_variant	Intron 10 of 11		XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5	c.1506+743A>G		intron_variant	Intron 10 of 11	1	NM_005443.5	ENSP00000265174.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23179 AN: 151922 Hom.: 3200 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.153 AC: 23233 AN: 152040 Hom.: 3210 Cov.: 32 AF XY: 0.146 AC XY: 10874 AN XY: 74342

African (AFR) AF: 0.373 AC: 15456 AN: 41386

American (AMR) AF: 0.0887 AC: 1356 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5158

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4824

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0689 AC: 4688 AN: 67996

Other (OTH) AF: 0.151 AC: 317 AN: 2102

Alfa AF: 0.0977 Hom.: 1563

Bravo AF: 0.168

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-1.2
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: rs2726659; hg19: chr4-108565215;