chr10-87659881-C-CGCTGCTGCT

Position:

• chr10-87659881-C-CGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001015880.2(PAPSS2):​c.-83_-75dupTGCTGCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (436 hom., cov: 0)
  • Exomes 𝑓: 0.0046 (98 hom.)
• Consequence: PAPSS2 NM_001015880.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 10-87659881-C-CGCTGCTGCT is Benign according to our data. Variant chr10-87659881-C-CGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 1274995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	1/13	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	1/12		NP_004661.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	1/13	1	NM_001015880.2	ENSP00000406157.1
PAPSS2	ENST00000361175	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	1/12	1		ENSP00000354436.4
ENSG00000196566	ENST00000354527.2	n.114_122dupAGCAGCAGC		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6408 AN: 151036 Hom.: 436 Cov.: 0

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0298

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000956

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000887

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.00463 AC: 4106 AN: 886490 Hom.: 98 Cov.: 14 AF XY: 0.00392 AC XY: 1805 AN XY: 460136

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00807

Gnomad4 ASJ exome AF: 0.000228

Gnomad4 EAS exome AF: 0.0000287

Gnomad4 SAS exome AF: 0.000583

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000459

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0425 AC: 6416 AN: 151140 Hom.: 436 Cov.: 0 AF XY: 0.0411 AC XY: 3034 AN XY: 73864

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0000956

Gnomad4 NFE AF: 0.000888

Gnomad4 OTH AF: 0.0269

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 04, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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;