ENST00000375544.7:c.150_155dupTGATGA

Variant names:

• chr9-92474742-C-CTCATCA
• rs3078372
• NM_017680.6:c.150_155dupTGATGA

Variant summary

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

The ENST00000375544.7(ASPN):​c.150_155dupTGATGA​(p.Asp50_Asp51dup) variant causes a disruptive inframe insertion change. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (444 hom., cov: 0)
  • Exomes 𝑓: 0.073 (2003 hom.)
• Consequence: ASPN ENST00000375544.7 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter 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: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000375544.7
• BP6: Variant 9-92474742-C-CTCATCA is Benign according to our data. Variant chr9-92474742-C-CTCATCA is described in ClinVar as Benign. ClinVar VariationId is 1237100.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375544.7. 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.150_155dupTGATGA	p.Asp50_Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+94922_564+94927dupATCATC		intron	N/A	NP_001012267.1	Q6IPU0-1
	ASPN	NM_001193335.3		c.150_155dupTGATGA	p.Asp50_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.150_155dupTGATGA	p.Asp50_Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	ENSP00000364694.3	Q9BXN1
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+94922_564+94927dupATCATC		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	ASPN	ENST00000907468.1		c.150_155dupTGATGA	p.Asp50_Asp51dup	disruptive_inframe_insertion	Exon 3 of 9	ENSP00000577527.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 10723 AN: 147504 Hom.: 444 Cov.: 0

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.0490

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0502

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.0645

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0744

GnomAD4 exome AF: 0.0728 AC: 100838 AN: 1385086 Hom.: 2003 Cov.: 0 AF XY: 0.0713 AC XY: 49141 AN XY: 689672

African (AFR) AF: 0.0844 AC: 2579 AN: 30566

American (AMR) AF: 0.0625 AC: 2565 AN: 41018

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 1700 AN: 24878

East Asian (EAS) AF: 0.0700 AC: 2636 AN: 37664

South Asian (SAS) AF: 0.0259 AC: 2112 AN: 81618

European-Finnish (FIN) AF: 0.0668 AC: 3374 AN: 50492

Middle Eastern (MID) AF: 0.0586 AC: 326 AN: 5562

European-Non Finnish (NFE) AF: 0.0775 AC: 81829 AN: 1055822

Other (OTH) AF: 0.0647 AC: 3717 AN: 57466

GnomAD4 genome AF: 0.0727 AC: 10735 AN: 147610 Hom.: 444 Cov.: 0 AF XY: 0.0717 AC XY: 5144 AN XY: 71758

African (AFR) AF: 0.0804 AC: 3189 AN: 39646

American (AMR) AF: 0.0654 AC: 960 AN: 14680

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 246 AN: 3430

East Asian (EAS) AF: 0.0505 AC: 252 AN: 4988

South Asian (SAS) AF: 0.0278 AC: 127 AN: 4562

European-Finnish (FIN) AF: 0.0673 AC: 670 AN: 9956

Middle Eastern (MID) AF: 0.0625 AC: 18 AN: 288

European-Non Finnish (NFE) AF: 0.0757 AC: 5082 AN: 67138

Other (OTH) AF: 0.0726 AC: 147 AN: 2024

Alfa AF: 0.0600 Hom.: 224

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=74/26	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;