3-64541041-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182920.2(ADAMTS9):c.5521+54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,604,902 control chromosomes in the GnomAD database, including 520,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (35793 hom., cov: 33)
  • Exomes 𝑓: 0.81 (485010 hom.)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-64541041-G-C is Benign according to our data. Variant chr3-64541041-G-C is described in ClinVar as [Benign]. Clinvar id is 1247158.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+54C>G		intron_variant		ENST00000498707.5
ADAMTS9	NM_001318781.2	c.5437+54C>G		intron_variant
ADAMTS9	XR_007095711.1	n.5780+54C>G		intron_variant, non_coding_transcript_variant
ADAMTS9	XR_245151.1	n.5864+54C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.5521+54C>G		intron_variant		1	NM_182920.2	P1
ADAMTS9	ENST00000295903.8	c.5437+54C>G		intron_variant		1
ADAMTS9	ENST00000481060.2	c.2688+54C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97542 AN: 151976 Hom.: 35792 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.666

GnomAD4 exome AF: 0.805 AC: 1169564 AN: 1452808 Hom.: 485010 AF XY: 0.809 AC XY: 583651 AN XY: 721794

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.849

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.752

Gnomad4 NFE exome AF: 0.856

Gnomad4 OTH exome AF: 0.777

GnomAD4 genome AF: 0.641 AC: 97551 AN: 152094 Hom.: 35793 Cov.: 33 AF XY: 0.634 AC XY: 47144 AN XY: 74346

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.664

Alfa AF: 0.735 Hom.: 5519

Bravo AF: 0.604

Asia WGS AF: 0.565 AC: 1968 AN: 3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.4
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs3796384; hg19: chr3-64526717; COSMIC: COSV55781666; COSMIC: COSV55781666;