rs370009530

Variant names:

• chr4-107614337-C-T
• rs370009530
• NM_005443.5:c.1787G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-107614337-C-T
• chr4-107614337-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005443.5(PAPSS1):​c.1787G>A​(p.Arg596Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PAPSS1 NM_005443.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS1	NM_005443.5	MANE Select	c.1787G>A	p.Arg596Gln	missense	Exon 12 of 12	NP_005434.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS1	ENST00000265174.5	TSL:1 MANE Select	c.1787G>A	p.Arg596Gln	missense	Exon 12 of 12	ENSP00000265174.4	O43252
	PAPSS1	ENST00000873396.1		c.1856G>A	p.Arg619Gln	missense	Exon 13 of 13	ENSP00000543455.1
	PAPSS1	ENST00000970503.1		c.1784G>A	p.Arg595Gln	missense	Exon 12 of 12	ENSP00000640562.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152070 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251128 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000369 AC: 54 AN: 1461660 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 727122

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111834

Other (OTH) AF: 0.0000497 AC: 3 AN: 60380

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152070 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.36
MVP		0.72
MPC		0.49
ClinPred		0.95	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.71
Mutation Taster		=32/68	disease causing

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: rs370009530; hg19: chr4-108535493;