rs3805346

Positions:

• chr4-107680880-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005443.5(PAPSS1):​c.669+1135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,156 control chromosomes in the GnomAD database, including 55,990 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 0.85 (55990 hom., cov: 31)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS1	NM_005443.5	c.669+1135G>A		intron_variant		ENST00000265174.5
PAPSS1	XM_011532400.3	c.606+1135G>A		intron_variant
PAPSS1	XM_011532401.2	c.606+1135G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS1	ENST00000265174.5	c.669+1135G>A		intron_variant		1	NM_005443.5	P1
PAPSS1	ENST00000502431.5	n.790+1135G>A		intron_variant, non_coding_transcript_variant		5
PAPSS1	ENST00000511304.5	n.361+1135G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128840 AN: 152036 Hom.: 55972 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.847 AC: 128909 AN: 152156 Hom.: 55990 Cov.: 31 AF XY: 0.854 AC XY: 63501 AN XY: 74388

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.961

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.849

Alfa AF: 0.910 Hom.: 29104

Bravo AF: 0.832

Asia WGS AF: 0.895 AC: 3113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.077
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs3805346; hg19: chr4-108602036;