10-87659881-CGCTGCTGCTGCT-CGCTGCTGCT

Variant names:

• chr10-87659881-CGCT-C
• rs3217087
• NM_001015880.2:c.-77_-75delTGC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001015880.2(PAPSS2):​c.-77_-75delTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,017,966 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (0 hom.)
• Consequence: PAPSS2 NM_001015880.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779

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]

ENSG00000196566 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000205 (31/151154) while in subpopulation AMR AF= 0.00158 (24/15204). AF 95% confidence interval is 0.00109. There are 1 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.-77_-75delTGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.-77_-75delTGC		5_prime_UTR_variant	Exon 1 of 12		NP_004661.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849	c.-77_-75delTGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001015880.2	ENSP00000406157.1
PAPSS2	ENST00000361175	c.-77_-75delTGC		5_prime_UTR_variant	Exon 1 of 12	1		ENSP00000354436.4
ENSG00000196566	ENST00000354527.2	n.120_122delAGC		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 31 AN: 151050 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

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: 0.0000740

Gnomad OTH AF: 0.000486

GnomAD4 exome AF: 0.00271 AC: 2351 AN: 866812 Hom.: 0 AF XY: 0.00254 AC XY: 1141 AN XY: 449938

Gnomad4 AFR exome AF: 0.00200

Gnomad4 AMR exome AF: 0.00209

Gnomad4 ASJ exome AF: 0.00117

Gnomad4 EAS exome AF: 0.00285

Gnomad4 SAS exome AF: 0.00160

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.00299

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.000205 AC: 31 AN: 151154 Hom.: 1 Cov.: 0 AF XY: 0.000244 AC XY: 18 AN XY: 73864

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000740

Gnomad4 OTH AF: 0.000481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3217087; hg19: chr10-89419638;