chr9-92474742-C-CTCA

Variant names:

• chr9-92474742-C-CTCA
• rs3078372
• NM_017680.6:c.153_155dupTGA

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_017680.6(ASPN):​c.153_155dupTGA​(p.Asp51dup) variant causes a disruptive inframe insertion change. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6793 hom., cov: 0)
  • Exomes 𝑓: 0.19 (13869 hom.)
• Consequence: ASPN NM_017680.6 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:2 O:2
• 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: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_017680.6
• BP6: Variant 9-92474742-C-CTCA is Benign according to our data. Variant chr9-92474742-C-CTCA is described in ClinVar as Benign. ClinVar VariationId is 2527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

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.153_155dupTGA	p.Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+94925_564+94927dupATC		intron	N/A	NP_001012267.1	Q6IPU0-1
	ASPN	NM_001193335.3		c.153_155dupTGA	p.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.153_155dupTGA	p.Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	ENSP00000364694.3	Q9BXN1
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+94925_564+94927dupATC		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	ASPN	ENST00000907468.1		c.153_155dupTGA	p.Asp51dup	disruptive_inframe_insertion	Exon 3 of 9	ENSP00000577527.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 39967 AN: 147386 Hom.: 6790 Cov.: 0

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.192 AC: 265438 AN: 1383238 Hom.: 13869 Cov.: 0 AF XY: 0.191 AC XY: 131736 AN XY: 688804

African (AFR) AF: 0.419 AC: 12809 AN: 30606

American (AMR) AF: 0.125 AC: 5132 AN: 40936

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6235 AN: 24860

East Asian (EAS) AF: 0.0380 AC: 1429 AN: 37616

South Asian (SAS) AF: 0.162 AC: 13184 AN: 81620

European-Finnish (FIN) AF: 0.168 AC: 8471 AN: 50388

Middle Eastern (MID) AF: 0.267 AC: 1484 AN: 5566

European-Non Finnish (NFE) AF: 0.194 AC: 204767 AN: 1054222

Other (OTH) AF: 0.208 AC: 11927 AN: 57424

GnomAD4 genome AF: 0.271 AC: 39995 AN: 147490 Hom.: 6793 Cov.: 0 AF XY: 0.265 AC XY: 18973 AN XY: 71698

African (AFR) AF: 0.481 AC: 19030 AN: 39602

American (AMR) AF: 0.176 AC: 2586 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 901 AN: 3430

East Asian (EAS) AF: 0.0335 AC: 167 AN: 4990

South Asian (SAS) AF: 0.151 AC: 690 AN: 4556

European-Finnish (FIN) AF: 0.181 AC: 1802 AN: 9942

Middle Eastern (MID) AF: 0.375 AC: 108 AN: 288

European-Non Finnish (NFE) AF: 0.205 AC: 13755 AN: 67092

Other (OTH) AF: 0.247 AC: 498 AN: 2020

Alfa AF: 0.208 Hom.: 224

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CENPP-related disorder (1)
-	-	1	not specified (1)
-	-	-	Lumbar disk degeneration, susceptibility to (1)
-	-	-	Osteoarthritis susceptibility 3 (1)

Computational scores

Source: dbNSFP v4.9

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

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3078372; hg19: chr9-95237024; COSMIC: COSV65016037;