Variant chr3-64522219-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182920.2(ADAMTS9):c.5760A>G(p.Gly1920=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,614,062 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 46 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 63 hom. )

Consequence

ADAMTS9
NM_182920.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.14

Variant links:

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]

ADAMTS9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-64522219-T-C is Benign according to our data. Variant chr3-64522219-T-C is described in ClinVar as [Benign]. Clinvar id is 791933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

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
ADAMTS9	NM_182920.2 linkuse as main transcript	c.5760A>G	p.Gly1920=	synonymous_variant	39/40	ENST00000498707.5	NP_891550.1
ADAMTS9	NM_001318781.2 linkuse as main transcript	c.5676A>G	p.Gly1892=	synonymous_variant	38/39		NP_001305710.1
ADAMTS9	XR_007095711.1 linkuse as main transcript	n.6019A>G		non_coding_transcript_exon_variant	38/40
ADAMTS9	XR_245151.1 linkuse as main transcript	n.6103A>G		non_coding_transcript_exon_variant	39/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS9	ENST00000498707.5 linkuse as main transcript	c.5760A>G	p.Gly1920=	synonymous_variant	39/40	1	NM_182920.2	ENSP00000418735	P1	Q9P2N4-3

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2248

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0518

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00396

AC:

995

AN:

251380

Hom.:

AF XY:

0.00309

AC XY:

420

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0527

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00171

AC:

2504

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1105

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0547

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.0149

AC:

2265

AN:

152332

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1116

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0521

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00733

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 07, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over