4-107614179-C-T

Position:

• chr4-107614179-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.*70G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,462,762 control chromosomes in the GnomAD database, including 41,374 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 0.19 (3264 hom., cov: 32)
  • Exomes 𝑓: 0.24 (38110 hom.)
• Consequence: PAPSS1 NM_005443.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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]

PAPSS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPSS1	NM_005443.5	c.*70G>A		3_prime_UTR_variant	12/12	ENST00000265174.5	NP_005434.4
PAPSS1	XM_011532400.3	c.*70G>A		3_prime_UTR_variant	12/12		XP_011530702.1
PAPSS1	XM_011532401.2	c.*70G>A		3_prime_UTR_variant	12/12		XP_011530703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174	c.*70G>A		3_prime_UTR_variant	12/12	1	NM_005443.5	ENSP00000265174.4
PAPSS1	ENST00000514815.1	n.174+17452G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29030 AN: 151832 Hom.: 3257 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.235 AC: 308543 AN: 1310812 Hom.: 38110 Cov.: 17 AF XY: 0.233 AC XY: 151788 AN XY: 651424

Gnomad4 AFR exome AF: 0.0593

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.191 AC: 29047 AN: 151950 Hom.: 3264 Cov.: 32 AF XY: 0.192 AC XY: 14290 AN XY: 74262

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.214

Alfa AF: 0.228 Hom.: 8440

Bravo AF: 0.193

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.2
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9569; hg19: chr4-108535335; COSMIC: COSV54489280;