3-64540975-CCAATGTG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_182920.2(ADAMTS9):c.5521+113_5521+119del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,252,006 control chromosomes in the GnomAD database, including 396,062 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (35502 hom., cov: 0)
  • Exomes 𝑓: 0.79 (360560 hom.)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

Genes affected

ADAMTS9 (HGNC:13202): (ADAM metallopeptidase with thrombospondin type 1 motif 9) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. Members of the ADAMTS family have been implicated in the cleavage of proteoglycans, the control of organ shape during development, and the inhibition of angiogenesis. This gene is localized to chromosome 3p14.3-p14.2, an area known to be lost in hereditary renal tumors. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-64540975-CCAATGTG-C is Benign according to our data. Variant chr3-64540975-CCAATGTG-C is described in ClinVar as [Benign]. Clinvar id is 1264037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS9	NM_182920.2	c.5521+113_5521+119del		intron_variant		ENST00000498707.5
ADAMTS9	NM_001318781.2	c.5437+113_5437+119del		intron_variant
ADAMTS9	XR_007095711.1	n.5780+113_5780+119del		intron_variant, non_coding_transcript_variant
ADAMTS9	XR_245151.1	n.5864+113_5864+119del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.5521+113_5521+119del		intron_variant		1	NM_182920.2	P1
ADAMTS9	ENST00000295903.8	c.5437+113_5437+119del		intron_variant		1
ADAMTS9	ENST00000481060.2	c.2688+113_2688+119del		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 96915 AN: 151284 Hom.: 35503 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.794 AC: 874399 AN: 1100604 Hom.: 360560 AF XY: 0.798 AC XY: 438205 AN XY: 549202

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.768

GnomAD4 genome AF: 0.640 AC: 96918 AN: 151402 Hom.: 35502 Cov.: 0 AF XY: 0.633 AC XY: 46749 AN XY: 73910

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.663

Alfa AF: 0.577 Hom.: 1489

Bravo AF: 0.604

Asia WGS AF: 0.566 AC: 1968 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3841969; hg19: chr3-64526651;