rs2726673

Positions:

• chr4-107620126-A-C
• chr4-107620126-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.1737-5739T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,238 control chromosomes in the GnomAD database, including 1,680 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 0.11 (1680 hom., cov: 33)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.1737-5739T>G		intron_variant		ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.1674-5739T>G		intron_variant			XP_011530702.1
PAPSS1	XM_011532401.2	c.1674-5739T>G		intron_variant			XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5	c.1737-5739T>G		intron_variant		1	NM_005443.5	ENSP00000265174	P1
PAPSS1	ENST00000514815.1	n.174+11505T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16855 AN: 152120 Hom.: 1672 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0497

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.111 AC: 16900 AN: 152238 Hom.: 1680 Cov.: 33 AF XY: 0.107 AC XY: 7960 AN XY: 74436

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0275

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0497

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0616 Hom.: 427

Bravo AF: 0.125

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.76

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: rs2726673; hg19: chr4-108541282;