rs2726673

Variant names:

• chr4-107620126-A-C
• rs2726673
• NM_005443.5:c.1737-5739T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-107620126-A-C
• chr4-107620126-A-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.1737-5739T>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
• 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=-0.83).
• 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 rank	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.1737-5739T>G		intron_variant	Intron 11 of 11	ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.1674-5739T>G		intron_variant	Intron 11 of 11		XP_011530702.1
PAPSS1	XM_011532401.2	c.1674-5739T>G		intron_variant	Intron 11 of 11		XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5	c.1737-5739T>G		intron_variant	Intron 11 of 11	1	NM_005443.5	ENSP00000265174.4
PAPSS1	ENST00000514815.1	n.174+11505T>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.265 AC: 11001 AN: 41484

American (AMR) AF: 0.0716 AC: 1095 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5178

South Asian (SAS) AF: 0.0275 AC: 133 AN: 4828

European-Finnish (FIN) AF: 0.0189 AC: 201 AN: 10624

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0497 AC: 3379 AN: 68040

Other (OTH) AF: 0.120 AC: 253 AN: 2112

Alfa AF: 0.0739 Hom.: 1731

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
PhyloP100		-0.13
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: rs2726673; hg19: chr4-108541282;