3-64533318-T-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.5614-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 1,512,194 control chromosomes in the GnomAD database, including 710,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (69128 hom., cov: 32)
  • Exomes 𝑓: 0.97 (641138 hom.)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960

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=-0.89).
• BP6: Variant 3-64533318-T-C is Benign according to our data. Variant chr3-64533318-T-C is described in ClinVar as [Benign]. Clinvar id is 1265324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS9	NM_182920.2	c.5614-48A>G		intron_variant		ENST00000498707.5
ADAMTS9	NM_001318781.2	c.5530-48A>G		intron_variant
ADAMTS9	XR_007095711.1	n.5873-48A>G		intron_variant, non_coding_transcript_variant
ADAMTS9	XR_245151.1	n.5957-48A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.5614-48A>G		intron_variant		1	NM_182920.2	P1
ADAMTS9	ENST00000295903.8	c.5530-48A>G		intron_variant		1
ADAMTS9	ENST00000481060.2	c.2781-48A>G		intron_variant		2
ADAMTS9	ENST00000467257.5	c.16-48A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144891 AN: 152178 Hom.: 69068 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.991

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.951

GnomAD3 exomes AF: 0.972 AC: 239793 AN: 246770 Hom.: 116594 AF XY: 0.973 AC XY: 129669 AN XY: 133262

Gnomad AFR exome AF: 0.896

Gnomad AMR exome AF: 0.978

Gnomad ASJ exome AF: 0.958

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.987

Gnomad FIN exome AF: 0.992

Gnomad NFE exome AF: 0.969

Gnomad OTH exome AF: 0.968

GnomAD4 exome AF: 0.971 AC: 1320321 AN: 1359898 Hom.: 641138 Cov.: 20 AF XY: 0.971 AC XY: 662185 AN XY: 681842

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.976

Gnomad4 ASJ exome AF: 0.960

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.986

Gnomad4 FIN exome AF: 0.989

Gnomad4 NFE exome AF: 0.971

Gnomad4 OTH exome AF: 0.966

GnomAD4 genome AF: 0.952 AC: 145009 AN: 152296 Hom.: 69128 Cov.: 32 AF XY: 0.954 AC XY: 71032 AN XY: 74472

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.961

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 0.991

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.951

Alfa AF: 0.961 Hom.: 12523

Bravo AF: 0.947

Asia WGS AF: 0.991 AC: 3446 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.5
Dann	Benign	0.60

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: rs1017537; hg19: chr3-64518994;