5-65301532-T-C

Variant names:

• chr5-65301532-T-C
• rs10042323
• NM_197941.4:c.1224-1401A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197941.4(ADAMTS6):​c.1224-1401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,912 control chromosomes in the GnomAD database, including 21,208 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 0.53 (21208 hom., cov: 31)
• Consequence: ADAMTS6 NM_197941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 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.1224-1401A>G		intron	N/A	NP_922932.2
	ADAMTS6	NR_135689.2		n.2086-1401A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS6	ENST00000381055.8	TSL:1 MANE Select	c.1224-1401A>G		intron	N/A	ENSP00000370443.3
	ADAMTS6	ENST00000470597.5	TSL:1	n.1245-1401A>G		intron	N/A
	ADAMTS6	ENST00000381052.8	TSL:2	n.*350-1401A>G		intron	N/A	ENSP00000424377.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79918 AN: 151792 Hom.: 21179 Cov.: 31

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.527 AC: 80002 AN: 151912 Hom.: 21208 Cov.: 31 AF XY: 0.522 AC XY: 38733 AN XY: 74228

African (AFR) AF: 0.566 AC: 23463 AN: 41434

American (AMR) AF: 0.542 AC: 8270 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3466

East Asian (EAS) AF: 0.445 AC: 2289 AN: 5148

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4812

European-Finnish (FIN) AF: 0.474 AC: 4992 AN: 10540

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35501 AN: 67940

Other (OTH) AF: 0.505 AC: 1068 AN: 2114

Alfa AF: 0.517 Hom.: 8037

Bravo AF: 0.534

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.74
PhyloP100		-1.2
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: rs10042323; hg19: chr5-64597359;