chr5-65158356-T-C

Variant names:

• chr5-65158356-T-C
• rs1423351
• NM_197941.4:c.3245-6411A>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.3245-6411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,092 control chromosomes in the GnomAD database, including 44,380 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 0.76 (44380 hom., cov: 31)
• Consequence: ADAMTS6 NM_197941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS6	NM_197941.4	c.3245-6411A>G		intron_variant	Intron 24 of 24	ENST00000381055.8	NP_922932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS6	ENST00000381055.8	c.3245-6411A>G		intron_variant	Intron 24 of 24	1	NM_197941.4	ENSP00000370443.3
ADAMTS6	ENST00000314351.9	n.905-6411A>G		intron_variant	Intron 5 of 5	2
ADAMTS6	ENST00000381052.8	n.*2517-6411A>G		intron_variant	Intron 25 of 25	2		ENSP00000424377.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115245 AN: 151972 Hom.: 44339 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.758 AC: 115337 AN: 152092 Hom.: 44380 Cov.: 31 AF XY: 0.748 AC XY: 55592 AN XY: 74326

African (AFR) AF: 0.885 AC: 36737 AN: 41524

American (AMR) AF: 0.749 AC: 11451 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2562 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2744 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2736 AN: 4798

European-Finnish (FIN) AF: 0.663 AC: 6995 AN: 10558

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49573 AN: 67982

Other (OTH) AF: 0.770 AC: 1621 AN: 2106

Alfa AF: 0.762 Hom.: 5971

Bravo AF: 0.775

Asia WGS AF: 0.553 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		-0.81
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: rs1423351; hg19: chr5-64454183;