NM_197941.4:c.1933+3290G>T

Variant names:

• chr5-65238814-C-A
• rs13183791
• NM_197941.4:c.1933+3290G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ADAMTS6 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197941.4. 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
	ADAMTS6	NM_197941.4	MANE Select	c.1933+3290G>T		intron	N/A	NP_922932.2
	ADAMTS6	NR_135689.2		n.2941+3290G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS6	ENST00000381055.8	TSL:1 MANE Select	c.1933+3290G>T		intron	N/A	ENSP00000370443.3
	ADAMTS6	ENST00000470597.5	TSL:1	n.1812+3290G>T		intron	N/A
	ADAMTS6	ENST00000381052.8	TSL:2	n.*1205+3290G>T		intron	N/A	ENSP00000424377.1

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

African (AFR) AF: 0.00837 AC: 347 AN: 41480

American (AMR) AF: 0.0203 AC: 310 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0553 AC: 266 AN: 4814

European-Finnish (FIN) AF: 0.0790 AC: 832 AN: 10530

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3751 AN: 67952

Other (OTH) AF: 0.0299 AC: 63 AN: 2108

Alfa AF: 0.0498 Hom.: 116

Bravo AF: 0.0301

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs13183791; hg19: chr5-64534641;