rs13183791

Positions:

• chr5-65238814-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197941.4(ADAMTS6):​c.1933+3290G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 151,974 control chromosomes in the GnomAD database, including 162 homozygotes. 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: 𝑓 0.037 (162 hom., cov: 31)
• Consequence: ADAMTS6 NM_197941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

Genes affected

ADAMTS6 (HGNC:222): (ADAM metallopeptidase with thrombospondin type 1 motif 6) 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. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Expression of this gene may be regulated by the cytokine TNF-alpha. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS6	NM_197941.4	c.1933+3290G>T		intron_variant		ENST00000381055.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS6	ENST00000381055.8	c.1933+3290G>T		intron_variant		1	NM_197941.4	P1
ADAMTS6	ENST00000470597.5	n.1812+3290G>T		intron_variant, non_coding_transcript_variant		1
ADAMTS6	ENST00000381052.8	c.*1205+3290G>T		intron_variant, NMD_transcript_variant		2
ADAMTS6	ENST00000464680.6	n.1951+3290G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5672 AN: 151856 Hom.: 162 Cov.: 31

Gnomad AFR AF: 0.00839

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0373 AC: 5669 AN: 151974 Hom.: 162 Cov.: 31 AF XY: 0.0379 AC XY: 2813 AN XY: 74280

Gnomad4 AFR AF: 0.00837

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.0790

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0499 Hom.: 102

Bravo AF: 0.0301

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.7
DANN	Benign	0.73

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: rs13183791; hg19: chr5-64534641;