rs973213

Variant names:

• chr4-107659051-C-T
• rs973213
• NM_005443.5:c.783+908G>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.783+908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,262 control chromosomes in the GnomAD database, including 414 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 0.070 (414 hom., cov: 32)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.783+908G>A		intron_variant	Intron 6 of 11	ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.720+908G>A		intron_variant	Intron 6 of 11		XP_011530702.1
PAPSS1	XM_011532401.2	c.720+908G>A		intron_variant	Intron 6 of 11		XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5	c.783+908G>A		intron_variant	Intron 6 of 11	1	NM_005443.5	ENSP00000265174.4
PAPSS1	ENST00000511304.5	n.475+908G>A		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10666 AN: 152144 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0702 AC: 10689 AN: 152262 Hom.: 414 Cov.: 32 AF XY: 0.0673 AC XY: 5007 AN XY: 74446

African (AFR) AF: 0.0855 AC: 3553 AN: 41550

American (AMR) AF: 0.0596 AC: 911 AN: 15288

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

East Asian (EAS) AF: 0.105 AC: 542 AN: 5182

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4824

European-Finnish (FIN) AF: 0.0390 AC: 414 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0681 AC: 4631 AN: 68022

Other (OTH) AF: 0.0894 AC: 189 AN: 2114

Alfa AF: 0.0715 Hom.: 326

Bravo AF: 0.0731

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.58
PhyloP100		-0.96
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: rs973213; hg19: chr4-108580207;