12-43425495-G-C

Variant names:

• chr12-43425495-G-C
• rs10785430
• NM_025003.5:c.4284+19C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025003.5(ADAMTS20):​c.4284+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 11 publications found

Genes affected

ADAMTS20 (HGNC:17178): (ADAM metallopeptidase with thrombospondin type 1 motif 20) The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025003.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS20	NM_025003.5	MANE Select	c.4284+19C>G		intron	N/A	NP_079279.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS20	ENST00000389420.8	TSL:1 MANE Select	c.4284+19C>G		intron	N/A	ENSP00000374071.3
	ADAMTS20	ENST00000935091.1		c.4179+19C>G		intron	N/A	ENSP00000605150.1
	ADAMTS20	ENST00000553158.5	TSL:5	c.4284+19C>G		intron	N/A	ENSP00000448341.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1284928 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 627322

African (AFR) AF: 0.00 AC: 0 AN: 28116

American (AMR) AF: 0.00 AC: 0 AN: 28022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20148

East Asian (EAS) AF: 0.00 AC: 0 AN: 33576

South Asian (SAS) AF: 0.00 AC: 0 AN: 56440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5076

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1013506

Other (OTH) AF: 0.00 AC: 0 AN: 52014

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 37330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.35
PhyloP100		-0.17

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

Other links and lift over

dbSNP: rs10785430; hg19: chr12-43819298;