9-92474742-CTCATCATCATCATCATCATCATCA-CTCATCATCATCATCATCATCATCATCATCATCATCA

Variant names:

• chr9-92474742-C-CTCATCATCATCA
• rs3078372
• NM_017680.6:c.144_155dupTGATGATGATGA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_017680.6(ASPN):​c.144_155dupTGATGATGATGA​(p.Asp48_Asp51dup) variant causes a disruptive inframe insertion change. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0071 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0082 (34 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASPN NM_017680.6 disruptive_inframe_insertion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.52
• Publications: 9 publications found

Genes affected

ASPN (HGNC:14872): (asporin) This gene encodes a cartilage extracellular protein that is member of the small leucine-rich proteoglycan family. The encoded protein may regulate chondrogenesis by inhibiting transforming growth factor-beta 1-induced gene expression in cartilage. This protein also binds collagen and calcium and may induce collagen mineralization. Polymorphisms in the aspartic acid repeat region of this gene are associated with a susceptibility to osteoarthritis, and also with intervertebral disc disease. Alternative splicing of this gene results in multiple transcript variants.[provided by RefSeq, Jul 2014]

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_017680.6
• BP6: Variant 9-92474742-C-CTCATCATCATCA is Benign according to our data. Variant chr9-92474742-C-CTCATCATCATCA is described in ClinVar as Benign. ClinVar VariationId is 3033526.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017680.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPN	NM_017680.6	MANE Select	c.144_155dupTGATGATGATGA	p.Asp48_Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+94916_564+94927dupATCATCATCATC		intron	N/A	NP_001012267.1	Q6IPU0-1
	ASPN	NM_001193335.3		c.144_155dupTGATGATGATGA	p.Asp48_Asp51dup	disruptive_inframe_insertion	Exon 2 of 6	NP_001180264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPN	ENST00000375544.7	TSL:1	c.144_155dupTGATGATGATGA	p.Asp48_Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	ENSP00000364694.3	Q9BXN1
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+94916_564+94927dupATCATCATCATC		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	ASPN	ENST00000907468.1		c.144_155dupTGATGATGATGA	p.Asp48_Asp51dup	disruptive_inframe_insertion	Exon 3 of 9	ENSP00000577527.1

Frequencies

GnomAD3 genomes AF: 0.00711 AC: 1049 AN: 147580 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00281

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.00620

Gnomad ASJ AF: 0.00350

Gnomad EAS AF: 0.00200

Gnomad SAS AF: 0.00942

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00924

Gnomad OTH AF: 0.00649

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00824 AC: 11423 AN: 1386474 Hom.: 34 Cov.: 0 AF XY: 0.00838 AC XY: 5784 AN XY: 690336

African (AFR) AF: 0.00273 AC: 84 AN: 30714

American (AMR) AF: 0.00321 AC: 132 AN: 41068

Ashkenazi Jewish (ASJ) AF: 0.00293 AC: 73 AN: 24898

East Asian (EAS) AF: 0.00119 AC: 45 AN: 37702

South Asian (SAS) AF: 0.00977 AC: 798 AN: 81678

European-Finnish (FIN) AF: 0.0133 AC: 674 AN: 50502

Middle Eastern (MID) AF: 0.00466 AC: 26 AN: 5576

European-Non Finnish (NFE) AF: 0.00868 AC: 9178 AN: 1056814

Other (OTH) AF: 0.00718 AC: 413 AN: 57522

GnomAD4 genome AF: 0.00709 AC: 1047 AN: 147686 Hom.: 5 Cov.: 0 AF XY: 0.00737 AC XY: 529 AN XY: 71794

African (AFR) AF: 0.00280 AC: 111 AN: 39674

American (AMR) AF: 0.00620 AC: 91 AN: 14688

Ashkenazi Jewish (ASJ) AF: 0.00350 AC: 12 AN: 3432

East Asian (EAS) AF: 0.00200 AC: 10 AN: 4990

South Asian (SAS) AF: 0.00899 AC: 41 AN: 4562

European-Finnish (FIN) AF: 0.0147 AC: 146 AN: 9962

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00925 AC: 621 AN: 67166

Other (OTH) AF: 0.00642 AC: 13 AN: 2026

Alfa AF: 0.0106 Hom.: 224

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CENPP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=79/21	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3078372; hg19: chr9-95237024;