5-65301532-T-C

Position:

• chr5-65301532-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS6	NM_197941.4	c.1224-1401A>G		intron_variant		ENST00000381055.8	NP_922932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS6	ENST00000381055.8	c.1224-1401A>G		intron_variant		1	NM_197941.4	ENSP00000370443.3
ADAMTS6	ENST00000470597.5	n.1245-1401A>G		intron_variant		1
ADAMTS6	ENST00000381052.8	n.*350-1401A>G		intron_variant		2		ENSP00000424377.1
ADAMTS6	ENST00000464680.6	n.1242-1401A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.505

Alfa AF: 0.516 Hom.: 6361

Bravo AF: 0.534

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.74

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: rs10042323; hg19: chr5-64597359;