chr9-92474742-CTCATCA-C

Variant names:

• chr9-92474742-CTCATCA-C
• rs3078372
• NM_017680.6:c.150_155delTGATGA

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.150_155delTGATGA​(p.Asp50_Asp51del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0581 in 1,468,376 control chromosomes in the GnomAD database, including 2,230 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (255 hom., cov: 0)
  • Exomes 𝑓: 0.060 (1975 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-CTCATCA-C is Benign according to our data. Variant chr9-92474742-CTCATCA-C is described in ClinVar as Benign. ClinVar VariationId is 3910744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 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.150_155delTGATGA	p.Asp50_Asp51del	disruptive_inframe_deletion	Exon 2 of 8	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+94922_564+94927delATCATC		intron	N/A	NP_001012267.1	Q6IPU0-1
	ASPN	NM_001193335.3		c.150_155delTGATGA	p.Asp50_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.150_155delTGATGA	p.Asp50_Asp51del	disruptive_inframe_deletion	Exon 2 of 8	ENSP00000364694.3	Q9BXN1
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+94922_564+94927delATCATC		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	ASPN	ENST00000907468.1		c.150_155delTGATGA	p.Asp50_Asp51del	disruptive_inframe_deletion	Exon 3 of 9	ENSP00000577527.1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6530 AN: 147492 Hom.: 254 Cov.: 0

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0387

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.0495

GnomAD4 exome AF: 0.0596 AC: 78708 AN: 1320778 Hom.: 1975 AF XY: 0.0608 AC XY: 39993 AN XY: 657788

African (AFR) AF: 0.00868 AC: 265 AN: 30536

American (AMR) AF: 0.0341 AC: 1320 AN: 38690

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 2193 AN: 23826

East Asian (EAS) AF: 0.193 AC: 6616 AN: 34310

South Asian (SAS) AF: 0.0915 AC: 7137 AN: 78028

European-Finnish (FIN) AF: 0.0266 AC: 1265 AN: 47536

Middle Eastern (MID) AF: 0.0497 AC: 271 AN: 5450

European-Non Finnish (NFE) AF: 0.0555 AC: 55971 AN: 1007608

Other (OTH) AF: 0.0670 AC: 3670 AN: 54794

GnomAD4 genome AF: 0.0443 AC: 6538 AN: 147598 Hom.: 255 Cov.: 0 AF XY: 0.0438 AC XY: 3143 AN XY: 71750

African (AFR) AF: 0.0110 AC: 436 AN: 39666

American (AMR) AF: 0.0364 AC: 534 AN: 14688

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 309 AN: 3430

East Asian (EAS) AF: 0.180 AC: 896 AN: 4984

South Asian (SAS) AF: 0.0994 AC: 453 AN: 4558

European-Finnish (FIN) AF: 0.0222 AC: 220 AN: 9930

Middle Eastern (MID) AF: 0.0382 AC: 11 AN: 288

European-Non Finnish (NFE) AF: 0.0521 AC: 3497 AN: 67132

Other (OTH) AF: 0.0534 AC: 108 AN: 2024

Alfa AF: 0.0837 Hom.: 224

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=192/8	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: COSV65016575;