chr4-107615229-G-A

Variant names:

• chr4-107615229-G-A
• rs2726670
• NM_005443.5:c.1737-842C>T

Variant summary

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

The NM_005443.5(PAPSS1):​c.1737-842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,886 control chromosomes in the GnomAD database, including 7,594 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 0.32 (7594 hom., cov: 31)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005443.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS1	NM_005443.5	MANE Select	c.1737-842C>T		intron	N/A	NP_005434.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS1	ENST00000265174.5	TSL:1 MANE Select	c.1737-842C>T		intron	N/A	ENSP00000265174.4
	PAPSS1	ENST00000873396.1		c.1806-842C>T		intron	N/A	ENSP00000543455.1
	PAPSS1	ENST00000970503.1		c.1734-842C>T		intron	N/A	ENSP00000640562.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47804 AN: 151768 Hom.: 7571 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.315 AC: 47863 AN: 151886 Hom.: 7594 Cov.: 31 AF XY: 0.313 AC XY: 23210 AN XY: 74214

African (AFR) AF: 0.302 AC: 12505 AN: 41402

American (AMR) AF: 0.329 AC: 5026 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2569 AN: 5168

South Asian (SAS) AF: 0.201 AC: 964 AN: 4802

European-Finnish (FIN) AF: 0.300 AC: 3157 AN: 10538

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21463 AN: 67936

Other (OTH) AF: 0.355 AC: 749 AN: 2108

Alfa AF: 0.291 Hom.: 3872

Bravo AF: 0.327

Asia WGS AF: 0.335 AC: 1164 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.78
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2726670; hg19: chr4-108536385;