chr4-107671509-C-T

Variant names:

• chr4-107671509-C-T
• rs4956024
• NM_005443.5:c.669+10506G>A

Variant summary

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

The NM_005443.5(PAPSS1):​c.669+10506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,926 control chromosomes in the GnomAD database, including 2,940 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 0.18 (2940 hom., cov: 32)
• Consequence: PAPSS1 NM_005443.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.669+10506G>A		intron_variant	Intron 5 of 11	ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.606+10506G>A		intron_variant	Intron 5 of 11		XP_011530702.1
PAPSS1	XM_011532401.2	c.606+10506G>A		intron_variant	Intron 5 of 11		XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5	c.669+10506G>A		intron_variant	Intron 5 of 11	1	NM_005443.5	ENSP00000265174.4
PAPSS1	ENST00000502431.5	n.790+10506G>A		intron_variant	Intron 5 of 5	5
PAPSS1	ENST00000511304.5	n.361+10506G>A		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27556 AN: 151808 Hom.: 2933 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.182 AC: 27575 AN: 151926 Hom.: 2940 Cov.: 32 AF XY: 0.184 AC XY: 13630 AN XY: 74232

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.207

Alfa AF: 0.206 Hom.: 3364

Bravo AF: 0.184

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.61

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: rs4956024; hg19: chr4-108592665;