10-87683553-T-C

Position:

• chr10-87683553-T-C

Variant summary

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

The NM_001015880.2(PAPSS2):​c.27+23545T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,110 control chromosomes in the GnomAD database, including 8,771 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 0.33 (8771 hom., cov: 32)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961

Genes affected

PAPSS2 (HGNC:8604): (3'-phosphoadenosine 5'-phosphosulfate synthase 2) Sulfation is a common modification of endogenous (lipids, proteins, and carbohydrates) and exogenous (xenobiotics and drugs) compounds. In mammals, the sulfate source is 3'-phosphoadenosine 5'-phosphosulfate (PAPS), created from ATP and inorganic sulfate. Two different tissue isoforms encoded by different genes synthesize PAPS. This gene encodes one of the two PAPS synthetases. Defects in this gene cause the Pakistani type of spondyloepimetaphyseal dysplasia. Two alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.27+23545T>C		intron_variant		ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.27+23545T>C		intron_variant			NP_004661.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849.2	c.27+23545T>C		intron_variant		1	NM_001015880.2	ENSP00000406157.1
PAPSS2	ENST00000361175.8	c.27+23545T>C		intron_variant		1		ENSP00000354436.4
PAPSS2	ENST00000465996.5	n.49+23148T>C		intron_variant		2
PAPSS2	ENST00000482258.1	n.70+22500T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49691 AN: 151992 Hom.: 8774 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.327 AC: 49703 AN: 152110 Hom.: 8771 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74354

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.326

Alfa AF: 0.377 Hom.: 11926

Bravo AF: 0.321

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.25
DANN	Benign	0.41

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: rs10887741; hg19: chr10-89443310;