rs2726165

Positions:

• chr4-107601860-C-T

Variant summary

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

The ENST00000514815.1(PAPSS1):​n.175-11463G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,048 control chromosomes in the GnomAD database, including 772 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 0.085 (772 hom., cov: 31)
• Consequence: PAPSS1 ENST00000514815.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS1	ENST00000514815.1	n.175-11463G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12854 AN: 151930 Hom.: 769 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0987

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

GnomAD4 genome AF: 0.0847 AC: 12881 AN: 152048 Hom.: 772 Cov.: 31 AF XY: 0.0816 AC XY: 6064 AN XY: 74342

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.0747

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0657 Hom.: 219

Bravo AF: 0.0930

Asia WGS AF: 0.0880 AC: 304 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2726165; hg19: chr4-108523016;