chr3-64532946-G-A

Position:

• chr3-64532946-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182920.2(ADAMTS9):​c.5718+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 152,194 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.015 (51 hom., cov: 32)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.13

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-64532946-G-A is Benign according to our data. Variant chr3-64532946-G-A is described in ClinVar as [Benign]. Clinvar id is 1227721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS9	NM_182920.2	c.5718+220C>T		intron_variant		ENST00000498707.5	NP_891550.1
ADAMTS9	NM_001318781.2	c.5634+220C>T		intron_variant			NP_001305710.1
ADAMTS9	XR_007095711.1	n.5977+220C>T		intron_variant, non_coding_transcript_variant
ADAMTS9	XR_245151.1	n.6061+220C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.5718+220C>T		intron_variant		1	NM_182920.2	ENSP00000418735	P1
ADAMTS9	ENST00000295903.8	c.5634+220C>T		intron_variant		1		ENSP00000295903
ADAMTS9	ENST00000481060.2	c.2885+220C>T		intron_variant		2		ENSP00000417521
ADAMTS9	ENST00000467257.5	c.120+220C>T		intron_variant, NMD_transcript_variant		5		ENSP00000478086

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2279 AN: 152076 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0150 AC: 2278 AN: 152194 Hom.: 51 Cov.: 32 AF XY: 0.0143 AC XY: 1067 AN XY: 74432

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.000919 Hom.: 0

Bravo AF: 0.0172

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.030
DANN	Benign	0.75

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: rs57662484; hg19: chr3-64518622;