9-92474742-CTCATCATCATCATCATCATCATCA-CTCATCATCATCATCATCATCA

Variant names:

• chr9-92474742-CTCA-C
• rs3078372
• NM_017680.6:c.153_155delTGA

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_155delTGA​(p.Asp51del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.439 in 1,532,104 control chromosomes in the GnomAD database, including 124,043 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (13265 hom., cov: 0)
  • Exomes 𝑓: 0.44 (110778 hom.)
• Consequence: ASPN NM_017680.6 disruptive_inframe_deletion
• 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 NM_017680.6
• BP6: Variant 9-92474742-CTCA-C is Benign according to our data. Variant chr9-92474742-CTCA-C is described in ClinVar as Benign. ClinVar VariationId is 1302755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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_155delTGA	p.Asp51del	disruptive_inframe_deletion	Exon 2 of 8	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+94925_564+94927delATC		intron	N/A	NP_001012267.1	Q6IPU0-1
	ASPN	NM_001193335.3		c.153_155delTGA	p.Asp51del	disruptive_inframe_deletion	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_155delTGA	p.Asp51del	disruptive_inframe_deletion	Exon 2 of 8	ENSP00000364694.3	Q9BXN1
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+94925_564+94927delATC		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	ASPN	ENST00000907468.1		c.153_155delTGA	p.Asp51del	disruptive_inframe_deletion	Exon 3 of 9	ENSP00000577527.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 58957 AN: 147384 Hom.: 13258 Cov.: 0

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.281

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.444 AC: 614369 AN: 1384612 Hom.: 110778 AF XY: 0.443 AC XY: 305192 AN XY: 689324

African (AFR) AF: 0.164 AC: 5010 AN: 30608

American (AMR) AF: 0.493 AC: 20141 AN: 40878

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 10019 AN: 24872

East Asian (EAS) AF: 0.560 AC: 21083 AN: 37648

South Asian (SAS) AF: 0.413 AC: 33572 AN: 81308

European-Finnish (FIN) AF: 0.493 AC: 24856 AN: 50406

Middle Eastern (MID) AF: 0.384 AC: 2134 AN: 5562

European-Non Finnish (NFE) AF: 0.448 AC: 472682 AN: 1055896

Other (OTH) AF: 0.433 AC: 24872 AN: 57434

GnomAD4 genome AF: 0.400 AC: 58985 AN: 147492 Hom.: 13265 Cov.: 0 AF XY: 0.405 AC XY: 29010 AN XY: 71690

African (AFR) AF: 0.178 AC: 7040 AN: 39626

American (AMR) AF: 0.476 AC: 6982 AN: 14668

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1488 AN: 3430

East Asian (EAS) AF: 0.640 AC: 3192 AN: 4986

South Asian (SAS) AF: 0.448 AC: 2042 AN: 4554

European-Finnish (FIN) AF: 0.517 AC: 5136 AN: 9926

Middle Eastern (MID) AF: 0.274 AC: 79 AN: 288

European-Non Finnish (NFE) AF: 0.476 AC: 31940 AN: 67098

Other (OTH) AF: 0.412 AC: 832 AN: 2018

Alfa AF: 0.430 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		=81/19	polymorphism (auto)

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

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: COSV106064296;