rs4956112

Positions:

• chr4-107631447-A-T

Variant summary

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

The NM_005443.5(PAPSS1):​c.1736+184T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,096 control chromosomes in the GnomAD database, including 4,425 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 0.24 (4425 hom., cov: 32)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS1	NM_005443.5	c.1736+184T>A		intron_variant		ENST00000265174.5
PAPSS1	XM_011532400.3	c.1673+184T>A		intron_variant
PAPSS1	XM_011532401.2	c.1673+184T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS1	ENST00000265174.5	c.1736+184T>A		intron_variant		1	NM_005443.5	P1
PAPSS1	ENST00000514815.1	n.174+184T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36527 AN: 151978 Hom.: 4410 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.241 AC: 36581 AN: 152096 Hom.: 4425 Cov.: 32 AF XY: 0.240 AC XY: 17814 AN XY: 74330

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.249

Alfa AF: 0.234 Hom.: 535

Bravo AF: 0.248

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.69

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: rs4956112; hg19: chr4-108552603;