3-64540936-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.5521+159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,222 control chromosomes in the GnomAD database, including 909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.063 (909 hom., cov: 34)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132

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=-0.94).
• BP6: Variant 3-64540936-T-C is Benign according to our data. Variant chr3-64540936-T-C is described in ClinVar as [Benign]. Clinvar id is 1251849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS9	NM_182920.2	c.5521+159A>G		intron_variant		ENST00000498707.5
ADAMTS9	NM_001318781.2	c.5437+159A>G		intron_variant
ADAMTS9	XR_007095711.1	n.5780+159A>G		intron_variant, non_coding_transcript_variant
ADAMTS9	XR_245151.1	n.5864+159A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.5521+159A>G		intron_variant		1	NM_182920.2	P1
ADAMTS9	ENST00000295903.8	c.5437+159A>G		intron_variant		1
ADAMTS9	ENST00000481060.2	c.2688+159A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9514 AN: 152104 Hom.: 902 Cov.: 34

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.0623

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

GnomAD4 genome AF: 0.0626 AC: 9533 AN: 152222 Hom.: 909 Cov.: 34 AF XY: 0.0662 AC XY: 4928 AN XY: 74430

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.00535

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0323 Hom.: 59

Bravo AF: 0.0870

Asia WGS AF: 0.102 AC: 354 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 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.87
Dann	Benign	0.44

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: rs9848764; hg19: chr3-64526612;