4-107597943-A-G

Variant names:

• chr4-107597943-A-G
• rs9332468
• ENST00000514815.1:n.175-7546T>C

Variant summary

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

The ENST00000514815.1(PAPSS1):​n.175-7546T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,142 control chromosomes in the GnomAD database, including 5,998 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 0.28 (5998 hom., cov: 32)
• Consequence: PAPSS1 ENST00000514815.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000514815.1	n.175-7546T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42642 AN: 152024 Hom.: 5980 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.281 AC: 42700 AN: 152142 Hom.: 5998 Cov.: 32 AF XY: 0.280 AC XY: 20826 AN XY: 74384

African (AFR) AF: 0.282 AC: 11692 AN: 41492

American (AMR) AF: 0.327 AC: 4998 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3472

East Asian (EAS) AF: 0.383 AC: 1981 AN: 5166

South Asian (SAS) AF: 0.177 AC: 854 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3166 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 71 AN: 290

European-Non Finnish (NFE) AF: 0.269 AC: 18276 AN: 68000

Other (OTH) AF: 0.282 AC: 596 AN: 2112

Alfa AF: 0.270 Hom.: 1953

Bravo AF: 0.291

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.75
PhyloP100		0.37

Splicing

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

Other links and lift over

dbSNP: rs9332468; hg19: chr4-108519099;